Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multi...
Saved in:
| Published in | Nature medicine Vol. 27; no. 3; pp. 491 - 503 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.03.2021
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR–Cas9 deletion of
PPIA
or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors.
Integration of longitudinal single-cell analysis of relapsed and refractory multiple myeloma patients in a prospective clinical trial uncovers new pathways of drug resistance and identifies potential actionable targets. |
|---|---|
| AbstractList | Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR-Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors. Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR-Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors. Integration of longitudinal single-cell analysis of relapsed and refractory multiple myeloma patients in a prospective clinical trial uncovers new pathways of drug resistance and identifies potential actionable targets. Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR-Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors.Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR-Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors. Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR-Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors. Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR–Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors. Integration of longitudinal single-cell analysis of relapsed and refractory multiple myeloma patients in a prospective clinical trial uncovers new pathways of drug resistance and identifies potential actionable targets. |
| Audience | Academic |
| Author | Gatt, Moshe E. Rouvio, Ory Luttwak, Efrat Lavi, Noa Shlomi-Loubaton, Shir Laiba, Meirav Wang, Shuang-Yin Gur, Chamutal Amit, Ido Ganzel, Chezi Chubar, Evgeni Moshe, Adi Nemets, Anatoly Shpilberg, Ofer Weiner, Assaf David, Eyal Dally, Najib Li, Baoguo Cohen, Yael C. Zada, Mor Bornstein, Chamutal Shvetz, Olga Tadmor, Tamar Vaxman, Iuliana Pasvolsky, Oren Ballan, Mouna Avivi, Irit Jarchowcky-Dolberg, Osnat |
| AuthorAffiliation | 11 Hematology, Bnai Zion Medical Center, Haifa, Israel 12 Barzilai Medical Center, Ashkelon, Israel 3 Department of Immunology, Weizmann Institute, Rehovot, Israel 1 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 6 Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel 16 Institute of Hematology, Assuta Medical Centers, Tel Aviv, Israel 14 Hematology, Kaplan Medical Center, affiliated with Hadassah and Hebrew University Medical School, Rehovot, Israel 8 Soroka Medical Center, Be’er She’va, Israel 9 Hematology, Rabin Medical Center, Beilinson, Petah Tikva, Israel 2 Department of Hematology, Tel-Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel 4 Hematology Department, Hadassah, Hebrew University Medical Center, Jerusalem, Israel 13 Hematology Department, Meir Medical Center, Kfar Saba, Israel 15 Hematological Institute, Assuta Ashdod Medical Center, Ashdod, Israel 7 Hematology Unit, HaEmek Medical Center, Afula, Israel 17 Hematology, Rebecca Sieff Hospital |
| AuthorAffiliation_xml | – name: 16 Institute of Hematology, Assuta Medical Centers, Tel Aviv, Israel – name: 9 Hematology, Rabin Medical Center, Beilinson, Petah Tikva, Israel – name: 15 Hematological Institute, Assuta Ashdod Medical Center, Ashdod, Israel – name: 7 Hematology Unit, HaEmek Medical Center, Afula, Israel – name: 2 Department of Hematology, Tel-Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel – name: 3 Department of Immunology, Weizmann Institute, Rehovot, Israel – name: 4 Hematology Department, Hadassah, Hebrew University Medical Center, Jerusalem, Israel – name: 11 Hematology, Bnai Zion Medical Center, Haifa, Israel – name: 5 Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel – name: 10 Carmel Medical Center, Haifa, Israel – name: 12 Barzilai Medical Center, Ashkelon, Israel – name: 6 Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel – name: 13 Hematology Department, Meir Medical Center, Kfar Saba, Israel – name: 1 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel – name: 14 Hematology, Kaplan Medical Center, affiliated with Hadassah and Hebrew University Medical School, Rehovot, Israel – name: 8 Soroka Medical Center, Be’er She’va, Israel – name: 17 Hematology, Rebecca Sieff Hospital, Zefat, Israel |
| Author_xml | – sequence: 1 givenname: Yael C. orcidid: 0000-0002-9061-7287 surname: Cohen fullname: Cohen, Yael C. organization: Sackler Faculty of Medicine, Tel Aviv University, Department of Hematology, Tel-Aviv Sourasky (Ichilov) Medical Center – sequence: 2 givenname: Mor surname: Zada fullname: Zada, Mor organization: Sackler Faculty of Medicine, Tel Aviv University, Department of Immunology, Weizmann Institute – sequence: 3 givenname: Shuang-Yin orcidid: 0000-0001-9683-4103 surname: Wang fullname: Wang, Shuang-Yin organization: Department of Immunology, Weizmann Institute – sequence: 4 givenname: Chamutal surname: Bornstein fullname: Bornstein, Chamutal organization: Department of Immunology, Weizmann Institute – sequence: 5 givenname: Eyal surname: David fullname: David, Eyal organization: Department of Immunology, Weizmann Institute – sequence: 6 givenname: Adi surname: Moshe fullname: Moshe, Adi organization: Department of Immunology, Weizmann Institute – sequence: 7 givenname: Baoguo surname: Li fullname: Li, Baoguo organization: Department of Immunology, Weizmann Institute – sequence: 8 givenname: Shir surname: Shlomi-Loubaton fullname: Shlomi-Loubaton, Shir organization: Department of Immunology, Weizmann Institute – sequence: 9 givenname: Moshe E. surname: Gatt fullname: Gatt, Moshe E. organization: Hematology Department, Hadassah, Hebrew University Medical Center – sequence: 10 givenname: Chamutal surname: Gur fullname: Gur, Chamutal organization: Department of Immunology, Weizmann Institute, Hematology Department, Hadassah, Hebrew University Medical Center – sequence: 11 givenname: Noa surname: Lavi fullname: Lavi, Noa organization: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus – sequence: 12 givenname: Chezi orcidid: 0000-0002-1722-4807 surname: Ganzel fullname: Ganzel, Chezi organization: Department of Hematology, Shaare Zedek Medical Center – sequence: 13 givenname: Efrat orcidid: 0000-0003-0212-2135 surname: Luttwak fullname: Luttwak, Efrat organization: Sackler Faculty of Medicine, Tel Aviv University, Department of Hematology, Tel-Aviv Sourasky (Ichilov) Medical Center – sequence: 14 givenname: Evgeni surname: Chubar fullname: Chubar, Evgeni organization: Hematology Unit, HaEmek Medical Center – sequence: 15 givenname: Ory surname: Rouvio fullname: Rouvio, Ory organization: Soroka Medical Center – sequence: 16 givenname: Iuliana orcidid: 0000-0002-8390-064X surname: Vaxman fullname: Vaxman, Iuliana organization: Sackler Faculty of Medicine, Tel Aviv University, Hematology, Rabin Medical Center, Beilinson – sequence: 17 givenname: Oren surname: Pasvolsky fullname: Pasvolsky, Oren organization: Sackler Faculty of Medicine, Tel Aviv University, Hematology, Rabin Medical Center, Beilinson – sequence: 18 givenname: Mouna surname: Ballan fullname: Ballan, Mouna organization: Carmel Medical Center – sequence: 19 givenname: Tamar surname: Tadmor fullname: Tadmor, Tamar organization: Hematology, Bnai Zion Medical Center – sequence: 20 givenname: Anatoly surname: Nemets fullname: Nemets, Anatoly organization: Barzilai Medical Center – sequence: 21 givenname: Osnat surname: Jarchowcky-Dolberg fullname: Jarchowcky-Dolberg, Osnat organization: Hematology Department, Meir Medical Center – sequence: 22 givenname: Olga surname: Shvetz fullname: Shvetz, Olga organization: Hematology, Kaplan Medical Center, affiliated with Hadassah and Hebrew University Medical School – sequence: 23 givenname: Meirav surname: Laiba fullname: Laiba, Meirav organization: Hematological Institute, Assuta Ashdod Medical Center – sequence: 24 givenname: Ofer surname: Shpilberg fullname: Shpilberg, Ofer organization: Institute of Hematology, Assuta Medical Centers – sequence: 25 givenname: Najib surname: Dally fullname: Dally, Najib organization: Hematology, Rebecca Sieff Hospital – sequence: 26 givenname: Irit surname: Avivi fullname: Avivi, Irit organization: Sackler Faculty of Medicine, Tel Aviv University, Department of Hematology, Tel-Aviv Sourasky (Ichilov) Medical Center – sequence: 27 givenname: Assaf surname: Weiner fullname: Weiner, Assaf email: assaf.weiner@weizmann.ac.il organization: Department of Immunology, Weizmann Institute – sequence: 28 givenname: Ido orcidid: 0000-0003-2968-877X surname: Amit fullname: Amit, Ido email: ido.amit@weizmann.ac.il organization: Department of Immunology, Weizmann Institute |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33619369$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNk9tq3DAQhk1JaQ7tC_SiGAqlvXCqg21ZN4UQelgIBHqid0KWx7aCLDmW3O3e9smrzSbtblhCEUJC-v5fGmbmODmwzkKSPMfoFCNavfU5LjjOEIkTE0qy5aPkCBd5mWGGfhzEPWJVVvGiPEyOvb9CCFFU8CfJIaUl5rTkR8nvRQM26FYrGbSzqWvTCbz2QVoF6ShDv5Qrn0rbpKGHSY4wB63SIKcOgk-1jbiRo4cmHWYT9GggHVZg3CDXah3NfVRObu761GvbGcgUGJN6uJ7BqnjyNHncSuPh2e16knz78P7r-afs4vLj4vzsIlMsz0OGW9kwmcuKS17yNm9Q0SjM67ImjCJCsGIlVYrXqGgRyfNKQVVXqikRkkwVNT1J3m18x7keoFHxa5M0Ypz0IKeVcFKL3Rure9G5n4KVmDBOo8HrW4PJxc_7IAbt18FIC272guSclCXJKx7Rl_fQKzdPNoYnSIEwLRjlW1QnDQhtWxffVWtTcVYWBcOs4Hmksj1UBzamw8SKaHU83uFP9_BxNDBotVfwZkcQmQC_Qidn78Xiy-f_Zy-_77KvttgepAm9d2ZeF5rfBV9sZ-ZvSu7KNALVBlCT836CVigdbgo2hqaNwEisO0JsOkLEjhA3HSGWUUruSe_cHxTRjchH2HYw_UvfA6o_CFIeLA |
| CitedBy_id | crossref_primary_10_1016_j_bbrep_2023_101589 crossref_primary_10_1038_s41408_024_01096_6 crossref_primary_10_1111_ejh_13905 crossref_primary_10_3389_fmolb_2021_757024 crossref_primary_10_3390_cancers13235949 crossref_primary_10_1080_14737140_2024_2343114 crossref_primary_10_3324_haematol_2023_283533 crossref_primary_10_1038_s41389_022_00380_z crossref_primary_10_1016_j_mcpro_2023_100492 crossref_primary_10_1038_s42003_022_04216_9 crossref_primary_10_1038_s43018_023_00544_9 crossref_primary_10_3389_fgene_2023_1179859 crossref_primary_10_1016_j_hoc_2023_12_012 crossref_primary_10_1021_acs_jproteome_3c00832 crossref_primary_10_1016_j_ejcb_2023_151299 crossref_primary_10_1158_1078_0432_CCR_24_0545 crossref_primary_10_1186_s12920_023_01748_9 crossref_primary_10_1016_j_bioorg_2023_106873 crossref_primary_10_1038_s41467_024_48364_4 crossref_primary_10_59717_j_xinn_med_2023_100041 crossref_primary_10_1016_j_molcel_2023_10_019 crossref_primary_10_3389_fimmu_2021_713358 crossref_primary_10_3389_fonc_2022_899272 crossref_primary_10_3390_cancers15051526 crossref_primary_10_1016_j_hoc_2023_12_016 crossref_primary_10_1038_s44319_024_00184_9 crossref_primary_10_3390_cancers15061682 crossref_primary_10_1038_s41573_023_00688_4 crossref_primary_10_1021_acssensors_4c01634 crossref_primary_10_1016_j_isci_2024_110486 crossref_primary_10_1038_s41467_022_32145_y crossref_primary_10_1002_advs_202405861 crossref_primary_10_1177_17588359231221340 crossref_primary_10_3390_cells13171431 crossref_primary_10_3389_fimmu_2024_1393906 crossref_primary_10_1016_j_critrevonc_2024_104560 crossref_primary_10_3390_molecules27072201 crossref_primary_10_3389_fimmu_2022_897862 crossref_primary_10_1016_j_gendis_2023_101129 crossref_primary_10_1038_s41590_022_01309_9 crossref_primary_10_1038_s43018_023_00657_1 crossref_primary_10_3389_fimmu_2023_1265101 crossref_primary_10_3389_fdgth_2023_1324453 crossref_primary_10_3390_molecules29122779 crossref_primary_10_1016_j_cels_2022_12_012 crossref_primary_10_4103_ijh_ijh_6_23 crossref_primary_10_1038_s41388_024_03245_4 crossref_primary_10_1016_j_cell_2022_03_011 crossref_primary_10_1093_clinchem_hvab108 crossref_primary_10_1093_nar_gkac646 crossref_primary_10_1186_s40364_023_00502_8 crossref_primary_10_1016_j_immuni_2022_02_006 crossref_primary_10_1016_j_tranon_2023_101754 crossref_primary_10_1038_s43018_024_00757_6 crossref_primary_10_1038_s41375_022_01597_y crossref_primary_10_1038_s41598_024_65937_x crossref_primary_10_1007_s13402_024_00922_0 crossref_primary_10_1002_mco2_203 crossref_primary_10_1002_cam4_70477 crossref_primary_10_1097_HEP_0000000000000869 crossref_primary_10_1038_s41467_023_40584_4 crossref_primary_10_2174_1570180820666230125102954 crossref_primary_10_3389_fimmu_2024_1432841 crossref_primary_10_3389_fimmu_2024_1458638 crossref_primary_10_1038_s12276_022_00884_z crossref_primary_10_1038_s41569_025_01132_3 crossref_primary_10_1080_16078454_2025_2456649 crossref_primary_10_1007_s10238_024_01526_6 crossref_primary_10_1186_s12885_024_12993_1 crossref_primary_10_1016_j_ccell_2023_05_007 crossref_primary_10_1111_nyas_14976 crossref_primary_10_3390_ijms25116192 crossref_primary_10_1038_s41467_024_48327_9 crossref_primary_10_1097_HCO_0000000000001014 crossref_primary_10_3389_fddsv_2024_1474331 crossref_primary_10_1002_ctm2_757 crossref_primary_10_3390_genes12101629 crossref_primary_10_1186_s13073_021_01001_x crossref_primary_10_3390_ijms25168949 crossref_primary_10_1002_biof_2135 crossref_primary_10_1038_s41598_023_46508_y crossref_primary_10_1002_cbf_3869 crossref_primary_10_1038_s41598_022_17239_3 crossref_primary_10_1016_j_tranon_2022_101532 crossref_primary_10_1126_sciadv_abj3286 crossref_primary_10_1038_s43018_024_00756_7 crossref_primary_10_1111_joim_13423 crossref_primary_10_3390_diagnostics11091534 crossref_primary_10_1016_j_tig_2023_07_005 crossref_primary_10_32604_or_2023_030770 crossref_primary_10_1016_j_chembiol_2021_08_011 crossref_primary_10_1038_s44320_024_00045_6 crossref_primary_10_3389_fimmu_2024_1455383 crossref_primary_10_3389_fonc_2023_1110693 crossref_primary_10_1038_s41420_022_01094_2 crossref_primary_10_3892_mco_2023_2705 crossref_primary_10_1097_BS9_0000000000000172 crossref_primary_10_1515_medgen_2022_2156 crossref_primary_10_1038_s41568_022_00502_0 crossref_primary_10_1182_blood_2023019758 crossref_primary_10_1016_j_jpha_2023_08_014 crossref_primary_10_3389_fonc_2023_1240966 crossref_primary_10_1158_0008_5472_CAN_23_3005 crossref_primary_10_3390_biom12121855 crossref_primary_10_3390_cells14020148 crossref_primary_10_1002_hem3_70047 crossref_primary_10_3389_fimmu_2021_799206 crossref_primary_10_1002_ctm2_653 crossref_primary_10_3389_fonc_2022_1038329 crossref_primary_10_1158_2767_9764_CRC_24_0170 crossref_primary_10_1182_blood_2022015854 crossref_primary_10_1172_JCI159527 crossref_primary_10_3390_cancers14174082 crossref_primary_10_1016_j_xcrm_2024_101925 crossref_primary_10_1111_imj_16034 crossref_primary_10_1016_j_yamp_2022_06_002 crossref_primary_10_1186_s13578_023_00971_2 crossref_primary_10_1186_s12859_022_04861_1 crossref_primary_10_3389_fcell_2024_1500474 crossref_primary_10_7554_eLife_75340 crossref_primary_10_4251_wjgo_v16_i7_3118 crossref_primary_10_1038_s41467_024_50910_z crossref_primary_10_1038_s41401_025_01500_2 crossref_primary_10_1182_blood_2021014011 crossref_primary_10_1016_j_tips_2023_05_006 crossref_primary_10_1016_j_isci_2022_104781 crossref_primary_10_1038_d41573_021_00041_7 crossref_primary_10_1038_s41571_023_00816_4 crossref_primary_10_1038_s41571_021_00593_y crossref_primary_10_3390_cancers16030498 crossref_primary_10_1111_cpr_13517 crossref_primary_10_1186_s12943_022_01648_z crossref_primary_10_1016_j_drudis_2024_104224 crossref_primary_10_1038_s43018_024_00763_8 crossref_primary_10_3389_fonc_2022_1074726 crossref_primary_10_3390_ijms26052074 crossref_primary_10_1186_s12931_023_02443_0 crossref_primary_10_1016_j_molimm_2024_10_005 crossref_primary_10_1097_CM9_0000000000003116 crossref_primary_10_1093_nar_gkad1087 crossref_primary_10_1038_s43018_022_00447_1 crossref_primary_10_4049_jimmunol_2200744 crossref_primary_10_1038_s41591_021_01276_y crossref_primary_10_3390_ijms241813744 crossref_primary_10_1016_j_heliyon_2023_e18305 crossref_primary_10_3389_fcell_2021_723016 crossref_primary_10_3390_ijms24076683 |
| Cites_doi | 10.1016/j.drup.2014.12.001 10.3324/haematol.2011.043331 10.1136/jclinpath-2015-203414 10.1182/blood-2010-12-328252 10.1038/nature10762 10.1158/0008-5472.CAN-06-1759 10.1016/S1470-2045(16)30206-6 10.1016/j.drup.2019.100663 10.1006/mthe.2000.0103 10.1056/NEJMra1011442 10.1126/science.1247651 10.1016/j.ctrv.2010.08.008 10.1182/blood-2015-12-687749 10.1182/blood-2012-01-405985 10.1182/blood-2006-07-038430 10.1016/j.ctrv.2018.09.001 10.3816/CLM.2009.n.056 10.1016/S0162-3109(00)00192-2 10.1200/JCO.2007.13.8545 10.1182/blood-2018-99-114311 10.3892/ijo.2016.3516 10.3389/fimmu.2018.02134 10.1002/ajh.24131 10.1016/j.cell.2017.05.018 10.3324/haematol.2015.124651 10.1016/j.cell.2015.11.013 10.1007/s40265-017-0841-y 10.1182/blood.2018880930 10.1182/blood-2005-01-0034 10.1038/leu.2017.331 10.1016/j.cell.2018.09.009 10.1182/blood-2005-11-013458 10.1126/science.aao4277 10.1038/s41375-018-0362-z 10.1200/JCO.2017.35.15_suppl.8000 10.1186/s13059-019-1812-2 10.1111/imr.12233 10.1182/bloodadvances.2019000432 10.1038/cddis.2013.410 10.1158/1535-7163.MCT-12-0782 10.1038/s41589-019-0291-9 10.1038/s41591-018-0269-2 10.1016/j.clml.2019.10.014 10.1007/164_2017_10 10.1242/dev.181396 10.3109/10428194.2015.1121258 10.3324/haematol.2019.236588 10.5772/intechopen.77004 10.1002/cti2.1007 10.1002/ajh.25791 10.1177/147323001003800501 |
| ContentType | Journal Article |
| Copyright | The Author(s), under exclusive licence to Springer Nature America, Inc. 2021 COPYRIGHT 2021 Nature Publishing Group The Author(s), under exclusive licence to Springer Nature America, Inc. 2021. |
| Copyright_xml | – notice: The Author(s), under exclusive licence to Springer Nature America, Inc. 2021 – notice: COPYRIGHT 2021 Nature Publishing Group – notice: The Author(s), under exclusive licence to Springer Nature America, Inc. 2021. |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM IOV ISR 3V. 7QG 7QL 7QP 7QR 7T5 7TK 7TM 7TO 7U7 7U9 7X7 7XB 88A 88E 88I 8AO 8FD 8FE 8FH 8FI 8FJ 8FK 8G5 ABUWG AEUYN AFKRA AZQEC BBNVY BENPR BHPHI C1K CCPQU DWQXO FR3 FYUFA GHDGH GNUQQ GUQSH H94 HCIFZ K9. LK8 M0S M1P M2O M2P M7N M7P MBDVC P64 PHGZM PHGZT PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS Q9U RC3 7X8 5PM |
| DOI | 10.1038/s41591-021-01232-w |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed In Context: Opposing Viewpoints Gale In Context: Science ProQuest Central (Corporate) Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Immunology Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Toxicology Abstracts Virology and AIDS Abstracts ProQuest Health & Medical Collection (NC LIVE) ProQuest Central (purchase pre-March 2016) Biology Database (Alumni Edition) Medical Database (Alumni Edition) Science Database (Alumni Edition) ProQuest Pharma Collection Technology Research Database ProQuest SciTech Collection ProQuest Natural Science Journals Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Research Library ProQuest Central (Alumni) ProQuest One Sustainability (subscription) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection Environmental Sciences and Pollution Management ProQuest One ProQuest Central Engineering Research Database Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student ProQuest Research Library AIDS and Cancer Research Abstracts SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Biological Sciences ProQuest Health & Medical Collection Medical Database Research Library Science Database Algology Mycology and Protozoology Abstracts (Microbiology C) Biological Science Database Research Library (Corporate) Biotechnology and BioEngineering Abstracts ProQuest Central Premium ProQuest One Academic ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China ProQuest Central Basic Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Research Library Prep ProQuest Central Student Oncogenes and Growth Factors Abstracts ProQuest Central Essentials Nucleic Acids Abstracts SciTech Premium Collection ProQuest Central China Environmental Sciences and Pollution Management ProQuest One Applied & Life Sciences ProQuest One Sustainability Health Research Premium Collection Natural Science Collection Health & Medical Research Collection Biological Science Collection Chemoreception Abstracts ProQuest Central (New) ProQuest Medical Library (Alumni) Virology and AIDS Abstracts ProQuest Science Journals (Alumni Edition) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database Neurosciences Abstracts ProQuest Hospital Collection (Alumni) Biotechnology and BioEngineering Abstracts ProQuest Health & Medical Complete ProQuest One Academic UKI Edition Engineering Research Database ProQuest One Academic Calcium & Calcified Tissue Abstracts ProQuest One Academic (New) Technology Research Database ProQuest One Academic Middle East (New) ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest One Health & Nursing Research Library (Alumni Edition) ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Biology Journals (Alumni Edition) ProQuest Central ProQuest Health & Medical Research Collection Genetics Abstracts Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts ProQuest Research Library ProQuest Central Basic Toxicology Abstracts ProQuest Science Journals ProQuest SciTech Collection ProQuest Medical Library Animal Behavior Abstracts Immunology Abstracts ProQuest Central (Alumni) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic Research Library Prep |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 3 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Biology |
| EISSN | 1546-170X |
| EndPage | 503 |
| ExternalDocumentID | PMC7612793 A655717594 33619369 10_1038_s41591_021_01232_w |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GeographicLocations | Israel |
| GeographicLocations_xml | – name: Israel |
| GrantInformation_xml | – fundername: European Molecular Biology Organization (EMBO) grantid: ALTF 263‐2018 funderid: https://doi.org/10.13039/100004410 – fundername: Amgen (Amgen Inc.) funderid: https://doi.org/10.13039/100002429 – fundername: Howard Hughes Medical Institute |
| GroupedDBID | --- .-4 .55 .GJ 0R~ 123 1CY 29M 2FS 36B 39C 3O- 3V. 4.4 53G 5BI 5M7 5RE 5S5 70F 7X7 85S 88A 88E 88I 8AO 8FE 8FH 8FI 8FJ 8G5 8R4 8R5 AAEEF AARCD AAYOK AAYZH AAZLF ABAWZ ABCQX ABDBF ABDPE ABEFU ABJNI ABLJU ABOCM ABUWG ACBWK ACGFO ACGFS ACGOD ACIWK ACMJI ACPRK ACUHS ADBBV ADFRT AENEX AEUYN AFBBN AFKRA AFRAH AFSHS AGAYW AGCDD AGHTU AHBCP AHMBA AHOSX AHSBF AIBTJ ALFFA ALIPV ALMA_UNASSIGNED_HOLDINGS AMTXH ARMCB ASPBG AVWKF AXYYD AZFZN AZQEC B0M BBNVY BENPR BHPHI BKKNO BPHCQ BVXVI CCPQU CS3 DB5 DU5 DWQXO EAD EAP EBC EBD EBS EE. EJD EMB EMK EMOBN EPL ESX EXGXG F5P FEDTE FQGFK FSGXE FYUFA GNUQQ GUQSH GX1 HCIFZ HMCUK HVGLF HZ~ IAO IEA IH2 IHR IHW INH INR IOF IOV ISR ITC J5H L7B LGEZI LK8 LOTEE M0L M1P M2O M2P M7P MK0 N9A NADUK NNMJJ NXXTH O9- ODYON P2P PQQKQ PROAC PSQYO Q2X RIG RNS RNT RNTTT RVV SHXYY SIXXV SJN SNYQT SOJ SV3 TAE TAOOD TBHMF TDRGL TSG TUS UKHRP UQL X7M XJT YHZ ZGI ~8M AAYXX ABFSG ACMFV ACSTC AEZWR AFANA AFHIU AHWEU AIXLP ALPWD ATHPR CITATION PHGZM PHGZT AETEA CGR CUY CVF ECM EIF NFIDA NPM PJZUB PPXIY PQGLB AEIIB PMFND 7QG 7QL 7QP 7QR 7T5 7TK 7TM 7TO 7U7 7U9 7XB 8FD 8FK C1K FR3 H94 K9. M7N MBDVC P64 PKEHL PQEST PQUKI PRINS Q9U RC3 7X8 PUEGO 5PM |
| ID | FETCH-LOGICAL-c744t-1fad7a4a89a969f4d05dc19b6b2730221c763cc9b05f02448ce8b8cd600a7c5b3 |
| IEDL.DBID | 7X7 |
| ISSN | 1078-8956 1546-170X |
| IngestDate | Thu Aug 21 18:36:52 EDT 2025 Sun Aug 24 04:06:59 EDT 2025 Sat Aug 23 12:23:46 EDT 2025 Tue Jun 17 21:42:55 EDT 2025 Thu Jun 12 23:29:28 EDT 2025 Tue Jun 10 20:40:31 EDT 2025 Fri Jun 27 04:00:24 EDT 2025 Fri Jun 27 04:25:58 EDT 2025 Thu May 22 21:12:16 EDT 2025 Mon Jul 21 05:35:46 EDT 2025 Tue Jul 01 03:53:43 EDT 2025 Thu Apr 24 22:59:38 EDT 2025 Fri Feb 21 02:37:42 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 3 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c744t-1fad7a4a89a969f4d05dc19b6b2730221c763cc9b05f02448ce8b8cd600a7c5b3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors jointly supervised this work: Assaf Weiner, Ido Amit |
| ORCID | 0000-0002-9061-7287 0000-0001-9683-4103 0000-0002-1722-4807 0000-0003-2968-877X 0000-0003-0212-2135 0000-0002-8390-064X |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/7612793 |
| PMID | 33619369 |
| PQID | 2501357399 |
| PQPubID | 33975 |
| PageCount | 13 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_7612793 proquest_miscellaneous_2492662489 proquest_journals_2501357399 gale_infotracmisc_A655717594 gale_infotracgeneralonefile_A655717594 gale_infotracacademiconefile_A655717594 gale_incontextgauss_ISR_A655717594 gale_incontextgauss_IOV_A655717594 gale_healthsolutions_A655717594 pubmed_primary_33619369 crossref_citationtrail_10_1038_s41591_021_01232_w crossref_primary_10_1038_s41591_021_01232_w springer_journals_10_1038_s41591_021_01232_w |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2021-03-01 |
| PublicationDateYYYYMMDD | 2021-03-01 |
| PublicationDate_xml | – month: 03 year: 2021 text: 2021-03-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | New York |
| PublicationPlace_xml | – name: New York – name: United States |
| PublicationTitle | Nature medicine |
| PublicationTitleAbbrev | Nat Med |
| PublicationTitleAlternate | Nat Med |
| PublicationYear | 2021 |
| Publisher | Nature Publishing Group US Nature Publishing Group |
| Publisher_xml | – name: Nature Publishing Group US – name: Nature Publishing Group |
| References | Cohen (CR24) 2018; 175 Kyle, Rajkumar (CR1) 2009; 9 Medaglia (CR25) 2017; 358 Palumbo, Anderson (CR2) 2011; 364 Krishnan, Jaiswal, Brown, Luk, Bebawy (CR13) 2016; 49 Matsuda, Koyasu (CR45) 2000; 47 Kawano (CR23) 2015; 263 Klages, Zufferey, Trono (CR51) 2000; 2 Bergsagel (CR27) 2005; 106 Tsvetkov (CR39) 2019; 15 Krejcik (CR37) 2016; 128 CR5 CR8 CR7 Paul (CR49) 2015; 163 CR47 Nijhof, van de Donk, Zweegman, Lokhorst (CR4) 2018; 78 CR46 Niewerth (CR14) 2015; 18 Khoo (CR42) 2019; 134 Majithia (CR6) 2015; 90 Kumar (CR9) 2018; 32 Shaughnessy (CR32) 2011; 118 Jakubowiak (CR33) 2017; 35 Narayanan (CR18) 2020; 48 CR16 Vincenz, Jäger, O’Dwyer, Samali (CR19) 2013; 12 CR12 CR10 Kyu (CR44) 2007; 67 Robak, Drozdz, Szemraj, Robak (CR38) 2018; 70 Nigro, Pompilio, Capogrossi (CR43) 2013; 4 Zhan (CR28) 2006; 108 Landgren (CR34) 2018; 132 Van De Donk, Usmani (CR36) 2018; 9 Harding, Baughn, Kumar (CR15) 2019; 33 Ledergor (CR22) 2018; 24 Ling (CR20) 2012; 97 Nikesitch, Ling (CR17) 2016; 69 Baran (CR26) 2019; 20 Chari (CR35) 2017; 130 Yan (CR3) 2019; 3 Kumar (CR52) 2016; 17 Khan (CR29) 2015; 100 Jaitin (CR48) 2014; 343 CR21 Decaux (CR30) 2008; 26 Greaves, Maley (CR40) 2012; 481 Keats (CR41) 2012; 120 Keren-Shaul (CR50) 2017; 169 Shaughnessy (CR31) 2007; 109 van de Donk (CR11) 2011; 37 T Harding (1232_CR15) 2019; 33 NWCJ Van De Donk (1232_CR36) 2018; 9 S Matsuda (1232_CR45) 2000; 47 DA Jaitin (1232_CR48) 2014; 343 N Klages (1232_CR51) 2000; 2 P Nigro (1232_CR43) 2013; 4 M Cohen (1232_CR24) 2018; 175 PL Bergsagel (1232_CR27) 2005; 106 F Zhan (1232_CR28) 2006; 108 N Majithia (1232_CR6) 2015; 90 Y Baran (1232_CR26) 2019; 20 1232_CR21 M Greaves (1232_CR40) 2012; 481 JD Shaughnessy (1232_CR31) 2007; 109 JC Kyu (1232_CR44) 2007; 67 O Decaux (1232_CR30) 2008; 26 SK Kumar (1232_CR9) 2018; 32 H Keren-Shaul (1232_CR50) 2017; 169 Y Yan (1232_CR3) 2019; 3 1232_CR5 C Medaglia (1232_CR25) 2017; 358 JJ Keats (1232_CR41) 2012; 120 P Robak (1232_CR38) 2018; 70 R Khan (1232_CR29) 2015; 100 RA Kyle (1232_CR1) 2009; 9 S Kumar (1232_CR52) 2016; 17 1232_CR7 Y Kawano (1232_CR23) 2015; 263 1232_CR8 JD Shaughnessy (1232_CR32) 2011; 118 IS Nijhof (1232_CR4) 2018; 78 J Krejcik (1232_CR37) 2016; 128 WH Khoo (1232_CR42) 2019; 134 A Chari (1232_CR35) 2017; 130 1232_CR46 1232_CR47 AJ Jakubowiak (1232_CR33) 2017; 35 N Nikesitch (1232_CR17) 2016; 69 NWCJ van de Donk (1232_CR11) 2011; 37 SCW Ling (1232_CR20) 2012; 97 D Niewerth (1232_CR14) 2015; 18 O Landgren (1232_CR34) 2018; 132 G Ledergor (1232_CR22) 2018; 24 1232_CR16 P Tsvetkov (1232_CR39) 2019; 15 1232_CR12 1232_CR10 SR Krishnan (1232_CR13) 2016; 49 S Narayanan (1232_CR18) 2020; 48 L Vincenz (1232_CR19) 2013; 12 A Palumbo (1232_CR2) 2011; 364 F Paul (1232_CR49) 2015; 163 33664491 - Nat Med. 2021 Mar;27(3):375-376. doi: 10.1038/s41591-021-01276-y. |
| References_xml | – volume: 18 start-page: 18 year: 2015 end-page: 35 ident: CR14 article-title: Molecular basis of resistance to proteasome inhibitors in hematological malignancies publication-title: Drug Resist. Update doi: 10.1016/j.drup.2014.12.001 – volume: 97 start-page: 64 year: 2012 end-page: 72 ident: CR20 article-title: Response of myeloma to the proteasome inhibitor bortezomib is correlated with the unfolded protein response regulator XBP-1 publication-title: Haematologica doi: 10.3324/haematol.2011.043331 – volume: 69 start-page: 97 year: 2016 end-page: 101 ident: CR17 article-title: Molecular mechanisms in multiple myeloma drug resistance publication-title: J. Clin. Pathol doi: 10.1136/jclinpath-2015-203414 – volume: 118 start-page: 3512 year: 2011 end-page: 3524 ident: CR32 article-title: Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with total therapy 3 publication-title: Blood doi: 10.1182/blood-2010-12-328252 – volume: 481 start-page: 306 year: 2012 end-page: 313 ident: CR40 article-title: Clonal evolution in cancer publication-title: Nature doi: 10.1038/nature10762 – volume: 67 start-page: 3654 year: 2007 end-page: 3662 ident: CR44 article-title: Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia- and cisplatin-induced cell death publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-06-1759 – ident: CR16 – ident: CR12 – volume: 17 start-page: e328 year: 2016 end-page: e346 ident: CR52 article-title: International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(16)30206-6 – volume: 48 start-page: 100663 year: 2020 ident: CR18 article-title: Targeting the ubiquitin-proteasome pathway to overcome anti-cancer drug resistance publication-title: Drug Resist. Update doi: 10.1016/j.drup.2019.100663 – volume: 2 start-page: 170 year: 2000 end-page: 176 ident: CR51 article-title: A stable system for the high-titer production of multiply attenuated lentiviral vectors publication-title: Mol. Ther. doi: 10.1006/mthe.2000.0103 – ident: CR8 – volume: 130 start-page: 3110 year: 2017 ident: CR35 article-title: Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma (MMY1001): updated results from an open-label, phase 1b study publication-title: Blood – volume: 364 start-page: 1046 year: 2011 end-page: 1060 ident: CR2 article-title: Multiple myeloma publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1011442 – volume: 343 start-page: 776 year: 2014 end-page: 779 ident: CR48 article-title: Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types publication-title: Science doi: 10.1126/science.1247651 – volume: 37 start-page: 266 year: 2011 end-page: 283 ident: CR11 article-title: Treatment of relapsed and refractory multiple myeloma in the era of novel agents publication-title: Cancer Treatment Rev. doi: 10.1016/j.ctrv.2010.08.008 – ident: CR21 – ident: CR46 – volume: 128 start-page: 384 year: 2016 end-page: 394 ident: CR37 article-title: Daratumumab depletes CD38 immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma publication-title: Blood doi: 10.1182/blood-2015-12-687749 – volume: 120 start-page: 1067 year: 2012 end-page: 1076 ident: CR41 article-title: Clonal competition with alternating dominance in multiple myeloma publication-title: Blood doi: 10.1182/blood-2012-01-405985 – volume: 109 start-page: 2276 year: 2007 end-page: 2284 ident: CR31 article-title: A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1 publication-title: Blood doi: 10.1182/blood-2006-07-038430 – ident: CR5 – volume: 70 start-page: 199 year: 2018 end-page: 208 ident: CR38 article-title: Drug resistance in multiple myeloma publication-title: Cancer Treat. Rev. doi: 10.1016/j.ctrv.2018.09.001 – volume: 9 start-page: 278 year: 2009 end-page: 288 ident: CR1 article-title: Treatment of multiple myeloma: a comprehensive review publication-title: Clin. Lymphoma Myeloma doi: 10.3816/CLM.2009.n.056 – volume: 47 start-page: 119 year: 2000 end-page: 125 ident: CR45 article-title: Mechanisms of action of cyclosporine publication-title: Immunopharmacology doi: 10.1016/S0162-3109(00)00192-2 – volume: 26 start-page: 4798 year: 2008 end-page: 4805 ident: CR30 article-title: Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2007.13.8545 – volume: 132 start-page: 3281 year: 2018 ident: CR34 article-title: Bone marrow-based and longitudinal blood-based MRD tracking in newly diagnosed multiple myeloma patients treated with daratumumab, carfilzomib, lenalidomide and dexamethasone (DKRd): a correlative and clinical phase II study publication-title: Blood doi: 10.1182/blood-2018-99-114311 – ident: CR47 – volume: 49 start-page: 33 year: 2016 end-page: 50 ident: CR13 article-title: Multiple myeloma and persistence of drug resistance in the age of novel drugs (Review) publication-title: Int. J. Oncol. doi: 10.3892/ijo.2016.3516 – volume: 9 start-page: 2134 year: 2018 ident: CR36 article-title: CD38 antibodies in multiple myeloma: mechanisms of action and modes of resistance publication-title: Front. Immunol. doi: 10.3389/fimmu.2018.02134 – ident: CR10 – volume: 90 start-page: 981 year: 2015 end-page: 985 ident: CR6 article-title: Outcomes of primary refractory multiple myeloma and the impact of novel therapies publication-title: Am. J. Hematol. doi: 10.1002/ajh.24131 – volume: 169 start-page: 1276 year: 2017 end-page: 1290.e17 ident: CR50 article-title: A unique microglia type associated with restricting development of Alzheimer’s disease publication-title: Cell doi: 10.1016/j.cell.2017.05.018 – volume: 100 start-page: 1214 year: 2015 end-page: 1221 ident: CR29 article-title: Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG s0120) publication-title: Haematologica doi: 10.3324/haematol.2015.124651 – volume: 163 start-page: 1663 year: 2015 end-page: 1677 ident: CR49 article-title: Transcriptional heterogeneity and lineage commitment in myeloid progenitors publication-title: Cell doi: 10.1016/j.cell.2015.11.013 – volume: 78 start-page: 19 year: 2018 end-page: 37 ident: CR4 article-title: Current and new therapeutic strategies for relapsed and refractory multiple myeloma: an update publication-title: Drugs doi: 10.1007/s40265-017-0841-y – volume: 134 start-page: 30 year: 2019 end-page: 43 ident: CR42 article-title: A niche-dependent myeloid transcriptome signature defines dormant myeloma cells publication-title: Blood doi: 10.1182/blood.2018880930 – volume: 106 start-page: 296 year: 2005 end-page: 303 ident: CR27 article-title: Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma publication-title: Blood doi: 10.1182/blood-2005-01-0034 – volume: 32 start-page: 986 year: 2018 end-page: 995 ident: CR9 article-title: Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time publication-title: Leukemia doi: 10.1038/leu.2017.331 – volume: 175 start-page: 1031 year: 2018 end-page: 1044.e18 ident: CR24 article-title: Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting publication-title: Cell doi: 10.1016/j.cell.2018.09.009 – volume: 108 start-page: 2020 year: 2006 end-page: 2028 ident: CR28 article-title: The molecular classification of multiple myeloma publication-title: Blood doi: 10.1182/blood-2005-11-013458 – volume: 358 start-page: 1622 year: 2017 end-page: 1626 ident: CR25 article-title: Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq publication-title: Science doi: 10.1126/science.aao4277 – volume: 33 start-page: 863 year: 2019 end-page: 883 ident: CR15 article-title: & Van Ness, B. The future of myeloma precision medicine: integrating the compendium of known drug resistance mechanisms with emerging tumor profiling technologies publication-title: Leukemia doi: 10.1038/s41375-018-0362-z – volume: 35 start-page: 8000 year: 2017 ident: CR33 article-title: Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): an open-label, phase 1b study publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2017.35.15_suppl.8000 – volume: 20 start-page: 206 year: 2019 ident: CR26 article-title: MetaCell: analysis of single-cell RNA-seq data using K-nn graph partitions publication-title: Genome Biol. doi: 10.1186/s13059-019-1812-2 – volume: 263 start-page: 160 year: 2015 end-page: 172 ident: CR23 article-title: Targeting the bone marrow microenvironment in multiple myeloma publication-title: Immunol. Rev. doi: 10.1111/imr.12233 – volume: 3 start-page: 2895 year: 2019 end-page: 2904 ident: CR3 article-title: The impact of response kinetics for multiple myeloma in the era of novel agents publication-title: Blood Adv. doi: 10.1182/bloodadvances.2019000432 – volume: 4 start-page: e888 year: 2013 end-page: e888 ident: CR43 article-title: Cyclophilin A: a key player for human disease publication-title: Cell Death Dis. doi: 10.1038/cddis.2013.410 – volume: 12 start-page: 831 year: 2013 end-page: 843 ident: CR19 article-title: Endoplasmic reticulum stress and the unfolded protein response: targeting the Achilles heel of multiple myeloma publication-title: Mol. Cancer Therapeut. doi: 10.1158/1535-7163.MCT-12-0782 – ident: CR7 – volume: 15 start-page: 681 year: 2019 end-page: 689 ident: CR39 article-title: Mitochondrial metabolism promotes adaptation to proteotoxic stress publication-title: Nat. Chem. Biol. doi: 10.1038/s41589-019-0291-9 – volume: 24 start-page: 1867 year: 2018 end-page: 1876 ident: CR22 article-title: Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma publication-title: Nat. Med. doi: 10.1038/s41591-018-0269-2 – volume: 106 start-page: 296 year: 2005 ident: 1232_CR27 publication-title: Blood doi: 10.1182/blood-2005-01-0034 – volume: 47 start-page: 119 year: 2000 ident: 1232_CR45 publication-title: Immunopharmacology doi: 10.1016/S0162-3109(00)00192-2 – volume: 9 start-page: 278 year: 2009 ident: 1232_CR1 publication-title: Clin. Lymphoma Myeloma doi: 10.3816/CLM.2009.n.056 – volume: 33 start-page: 863 year: 2019 ident: 1232_CR15 publication-title: Leukemia doi: 10.1038/s41375-018-0362-z – volume: 481 start-page: 306 year: 2012 ident: 1232_CR40 publication-title: Nature doi: 10.1038/nature10762 – volume: 12 start-page: 831 year: 2013 ident: 1232_CR19 publication-title: Mol. Cancer Therapeut. doi: 10.1158/1535-7163.MCT-12-0782 – volume: 130 start-page: 3110 year: 2017 ident: 1232_CR35 publication-title: Blood – volume: 32 start-page: 986 year: 2018 ident: 1232_CR9 publication-title: Leukemia doi: 10.1038/leu.2017.331 – volume: 163 start-page: 1663 year: 2015 ident: 1232_CR49 publication-title: Cell doi: 10.1016/j.cell.2015.11.013 – volume: 37 start-page: 266 year: 2011 ident: 1232_CR11 publication-title: Cancer Treatment Rev. doi: 10.1016/j.ctrv.2010.08.008 – volume: 90 start-page: 981 year: 2015 ident: 1232_CR6 publication-title: Am. J. Hematol. doi: 10.1002/ajh.24131 – volume: 48 start-page: 100663 year: 2020 ident: 1232_CR18 publication-title: Drug Resist. Update doi: 10.1016/j.drup.2019.100663 – volume: 26 start-page: 4798 year: 2008 ident: 1232_CR30 publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2007.13.8545 – volume: 109 start-page: 2276 year: 2007 ident: 1232_CR31 publication-title: Blood doi: 10.1182/blood-2006-07-038430 – volume: 97 start-page: 64 year: 2012 ident: 1232_CR20 publication-title: Haematologica doi: 10.3324/haematol.2011.043331 – volume: 18 start-page: 18 year: 2015 ident: 1232_CR14 publication-title: Drug Resist. Update doi: 10.1016/j.drup.2014.12.001 – volume: 343 start-page: 776 year: 2014 ident: 1232_CR48 publication-title: Science doi: 10.1126/science.1247651 – ident: 1232_CR10 doi: 10.1016/j.clml.2019.10.014 – volume: 108 start-page: 2020 year: 2006 ident: 1232_CR28 publication-title: Blood doi: 10.1182/blood-2005-11-013458 – volume: 2 start-page: 170 year: 2000 ident: 1232_CR51 publication-title: Mol. Ther. doi: 10.1006/mthe.2000.0103 – volume: 15 start-page: 681 year: 2019 ident: 1232_CR39 publication-title: Nat. Chem. Biol. doi: 10.1038/s41589-019-0291-9 – volume: 17 start-page: e328 year: 2016 ident: 1232_CR52 publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(16)30206-6 – ident: 1232_CR16 doi: 10.1007/164_2017_10 – volume: 4 start-page: e888 year: 2013 ident: 1232_CR43 publication-title: Cell Death Dis. doi: 10.1038/cddis.2013.410 – volume: 49 start-page: 33 year: 2016 ident: 1232_CR13 publication-title: Int. J. Oncol. doi: 10.3892/ijo.2016.3516 – ident: 1232_CR21 doi: 10.1242/dev.181396 – volume: 118 start-page: 3512 year: 2011 ident: 1232_CR32 publication-title: Blood doi: 10.1182/blood-2010-12-328252 – volume: 24 start-page: 1867 year: 2018 ident: 1232_CR22 publication-title: Nat. Med. doi: 10.1038/s41591-018-0269-2 – ident: 1232_CR7 doi: 10.3109/10428194.2015.1121258 – volume: 175 start-page: 1031 year: 2018 ident: 1232_CR24 publication-title: Cell doi: 10.1016/j.cell.2018.09.009 – ident: 1232_CR8 doi: 10.3324/haematol.2019.236588 – volume: 358 start-page: 1622 year: 2017 ident: 1232_CR25 publication-title: Science doi: 10.1126/science.aao4277 – volume: 78 start-page: 19 year: 2018 ident: 1232_CR4 publication-title: Drugs doi: 10.1007/s40265-017-0841-y – ident: 1232_CR12 doi: 10.5772/intechopen.77004 – volume: 3 start-page: 2895 year: 2019 ident: 1232_CR3 publication-title: Blood Adv. doi: 10.1182/bloodadvances.2019000432 – volume: 134 start-page: 30 year: 2019 ident: 1232_CR42 publication-title: Blood doi: 10.1182/blood.2018880930 – ident: 1232_CR46 doi: 10.1002/cti2.1007 – volume: 20 start-page: 206 year: 2019 ident: 1232_CR26 publication-title: Genome Biol. doi: 10.1186/s13059-019-1812-2 – volume: 100 start-page: 1214 year: 2015 ident: 1232_CR29 publication-title: Haematologica doi: 10.3324/haematol.2015.124651 – volume: 120 start-page: 1067 year: 2012 ident: 1232_CR41 publication-title: Blood doi: 10.1182/blood-2012-01-405985 – volume: 132 start-page: 3281 year: 2018 ident: 1232_CR34 publication-title: Blood doi: 10.1182/blood-2018-99-114311 – volume: 9 start-page: 2134 year: 2018 ident: 1232_CR36 publication-title: Front. Immunol. doi: 10.3389/fimmu.2018.02134 – volume: 70 start-page: 199 year: 2018 ident: 1232_CR38 publication-title: Cancer Treat. Rev. doi: 10.1016/j.ctrv.2018.09.001 – ident: 1232_CR5 doi: 10.1002/ajh.25791 – volume: 263 start-page: 160 year: 2015 ident: 1232_CR23 publication-title: Immunol. Rev. doi: 10.1111/imr.12233 – volume: 128 start-page: 384 year: 2016 ident: 1232_CR37 publication-title: Blood doi: 10.1182/blood-2015-12-687749 – volume: 35 start-page: 8000 year: 2017 ident: 1232_CR33 publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2017.35.15_suppl.8000 – ident: 1232_CR47 doi: 10.1177/147323001003800501 – volume: 364 start-page: 1046 year: 2011 ident: 1232_CR2 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1011442 – volume: 67 start-page: 3654 year: 2007 ident: 1232_CR44 publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-06-1759 – volume: 169 start-page: 1276 year: 2017 ident: 1232_CR50 publication-title: Cell doi: 10.1016/j.cell.2017.05.018 – volume: 69 start-page: 97 year: 2016 ident: 1232_CR17 publication-title: J. Clin. Pathol doi: 10.1136/jclinpath-2015-203414 – reference: 33664491 - Nat Med. 2021 Mar;27(3):375-376. doi: 10.1038/s41591-021-01276-y. |
| SSID | ssj0003059 |
| Score | 2.6565099 |
| Snippet | Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease... |
| SourceID | pubmedcentral proquest gale pubmed crossref springer |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 491 |
| SubjectTerms | 631/250 631/67 Adult Aged Aged, 80 and over Antibodies, Monoclonal - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomedical and Life Sciences Biomedicine Bortezomib Cancer Cancer Research Case-Control Studies Cell proliferation Clinical trials CRISPR Dexamethasone Dexamethasone - administration & dosage Drug resistance Drug Resistance, Neoplasm Drug therapy Female Folding Gene sequencing Health services Heterogeneity Humans Hypoxia Immunotherapy Infectious Diseases Inhibitor drugs Lenalidomide - administration & dosage Male Metabolic Diseases Middle Aged Mitochondria Molecular dynamics Molecular Medicine Monoclonal antibodies Multiple myeloma Multiple Myeloma - drug therapy Multiple Myeloma - pathology Neoplasm Recurrence, Local Neurosciences Oligopeptides - administration & dosage Oncology, Experimental Patient outcomes Patients Peptidylprolyl isomerase Plasma cells Proteasome inhibitors Protein folding Proteins Relapse Safety Single-Cell Analysis - methods Survival Target recognition Therapeutic applications Therapeutic targets Treatment Outcome Tumor cells Tumors |
| Title | Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing |
| URI | https://link.springer.com/article/10.1038/s41591-021-01232-w https://www.ncbi.nlm.nih.gov/pubmed/33619369 https://www.proquest.com/docview/2501357399 https://www.proquest.com/docview/2492662489 https://pubmed.ncbi.nlm.nih.gov/PMC7612793 |
| Volume | 27 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3Nb9MwFLdgE4gLgvFVGMMgBAdmLU3sxDmhFq0aSCtoMNSb5Tj2mNQlhbSqeuUv573EzZYKJk6V4l-kxs_v0--DkNdhKoSNrWO5lZzxJOBMh86xMNEizICfIodxyONxfHTKP03ExAfcKp9WuZaJtaDOS4Mx8gNQ1f1IJKBP389-MpwahberfoTGTbKNrcswpSuZtA4XnuW0yTmUTIIj4ItmgkgeVKC4MOcnRGcarAq27CimTfF8RT9t5k5uXKDWeml0j9z1BiUdNCfgPrlhix1yqxkxudoht4_95fkD8rspynU-SkdLR8HXRvsRCE9xNPFSryqqi5xeqcqiTa54Rc8LioUvs8rmdJ2GSC9WdlpeaOrbs1bUz_2hGIKYWob3AtSna8OTh-R0dPjtwxHzIxiYSTifs77TeaK5lqlO49TxPBC56adZnIHZA-q_b0A-GZNmgXCg7bk0VmbS5GBG6cSILHpEtoqysE8INcZgr_s85oHjoRWp0EHinI4zsEjyUPZIf73_yvj-5DgmY6rqe_JIqoZmCmimapqpZY-8a9-ZNd05rkW_QLKqpsK0ZW01iIUAr1akvEde1QhsjFFg5s2ZXlSV-vj5-3-Avp50QG89yJXwFUb7agfYC2y41UG-6SDPmnbjfwPudoAgB0x3eX1alZdDlbrkmh552S7jm5hbV9hyARjsGRmHXALmcXO4282MInCwoxhWks6xbwHYnby7Upz_qLuUJ2A7g_Dvkf01g1z-rX_T6On1X_GM3AlrnsUkwF2yNf-1sM_BKpxnezXr75HtwWg4HMPv8HD85eQPkeRi-w |
| linkProvider | ProQuest |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Jb9NAFB6VVCwXBGULFDoglgNYdewZLweECrRqaBNQF9TbMB7PlEqpHXCiKFd-EL-R9-yxW0dQcek189mK5-0zbyHkuRdzrgNtnFRHzGGhyxzpGeN4oeReAvLkGzyHHAyD7UP26YgfLZHfdS0MplXWOrFU1Gmu8Ix8HUx1z-ch2NN34x8OTo3C29V6hEbFFjt6PoOQrXjb_wj0feF5W5sHH7YdO1XAUSFjE6dnZBpKJqNYxkFsWOryVPXiJEjAkoNF6ykQOaXixOUGDBiLlI6SSKXgGchQ8cSH914hy8yHUKZDlt9vDr_sNbofpCeushwjJ4LQw5bpuH60XoCpxCwjD8N38GOcWcsULhqEcxZxMVtz4cq2tIRbt8hN68LSjYrnbpMlna2Qq9VQy_kKuTaw1_V3yK-qDNjYc0GaGwrRPXqswGoUhyHP5LygMkvpuTowWmWnF_Qko1hqMy50SuvER3o616P8VFLbELagdtIQxUOPkXbwJoLaBHH45S45vBTy3COdLM_0A0KVUthdPw2Ya5inecylGxojgwR8oNSLuqRX779QtiM6DuYYifJm3o9ERTMBNBMlzcSsS143z4yrfiAXoteQrKKqaW2UidgIOIc4msesS56VCGzFkWGuz7GcFoXof_76H6D9vRbolQWZHL5CSVtfAXuBLb5ayJct5HHV4PxvwNUWEDSPai_X3Cqs5ivEmZx2ydNmGZ_EbL5M51PAYJfKwGMRYO5XzN1spu9DSO8HsBK22L4BYD_09kp28r3six6Ctw7mpkve1AJy9rf-TaOHF3_FGrm-fTDYFbv94c4jcsMr5RdTEFdJZ_Jzqh-DTzpJnlhFQMm3y9Y9fwCrOp4- |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1bb9MwFLbGENNeEIzLCoMZxOUBouZi5_KA0MSoVsYGAob6ZhzHHpO6pJBWVV_5Wfw6zkmcbKlg4mWv9Zeo8bnb50LIEz_hXIfaOJmOmcMilznSN8bxI8n9FOQpMHgOeXAY7h2xdyM-WiG_m1oYTKtsdGKlqLNC4Rl5H0y1F_AI7Gnf2LSIj7uD15MfDk6QwpvWZpxGzSL7ejGH8K18NdwFWj_1_cHbL2_2HDthwFERY1PHMzKLJJNxIpMwMSxzeaa8JA1TsOpg3TwF4qdUkrrcgDFjsdJxGqsMvAQZKZ4G8N4r5GoUcA9lLBq1wR7KUVLnO8ZODEGILdhxg7hfgtHEfCMfA3nwaJx5xygum4ZztnE5b3Pp8rayiYMb5Lp1ZulOzX03yYrON8i1erzlYoOsHdiL-1vkV10QbOwJIS0MhTgffVdgOopjkedyUVKZZ_RcRRit89RLepJTLLqZlDqjTQokPV3ocXEqqW0NW1I7c4ji8cdYO3gnQW2qOPxymxxdCnHukNW8yPUmoUop7LOfhcw1zNc84dKNjJFhCt5Q5sc94jX7L5TtjY4jOsaiuqMPYlHTTADNREUzMe-RF-0zk7ozyIXobSSrqKtbW7UidkLOIaLmCeuRxxUCm3LkyN7HclaWYvjh63-APn_qgJ5bkCngK5S0lRawF9jsq4N81kEe163O_wbc6gBBB6nucsOtwurAUpxJbI88apfxSczry3UxAwz2qwx9FgPmbs3c7WYGAQT3QQgrUYftWwB2Ru-u5Cffqw7pEfjtYHh65GUjIGd_6980unfxV2yTNdA44v3wcP8-Wfcr8cVcxC2yOv050w_AOZ2mDystQMm3y1Y7fwA_6KEO |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+resistance+pathways+and+therapeutic+targets+in+relapsed+multiple+myeloma+patients+through+single-cell+sequencing&rft.jtitle=Nature+medicine&rft.au=Cohen%2C+Yael+C&rft.au=Zada%2C+Mor&rft.au=Wang%2C+Shuang-Yin&rft.au=Bornstein%2C+Chamutal&rft.date=2021-03-01&rft.issn=1546-170X&rft.eissn=1546-170X&rft.volume=27&rft.issue=3&rft.spage=491&rft_id=info:doi/10.1038%2Fs41591-021-01232-w&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1078-8956&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1078-8956&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1078-8956&client=summon |