Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs e...

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Published inNature cell biology Vol. 22; no. 6; pp. 689 - 700
Main Authors Perry, John M., Tao, Fang, Roy, Anuradha, Lin, Tara, He, Xi C., Chen, Shiyuan, Lu, Xiuling, Nemechek, Jacqelyn, Ruan, Linhao, Yu, Xiazhen, Dukes, Debra, Moran, Andrea, Pace, Jennifer, Schroeder, Kealan, Zhao, Meng, Venkatraman, Aparna, Qian, Pengxu, Li, Zhenrui, Hembree, Mark, Paulson, Ariel, He, Zhiquan, Xu, Dong, Tran, Thanh-Huyen, Deshmukh, Prashant, Nguyen, Chi Thanh, Kasi, Rajeswari M., Ryan, Robin, Broward, Melinda, Ding, Sheng, Guest, Erin, August, Keith, Gamis, Alan S., Godwin, Andrew, Sittampalam, G. Sitta, Weir, Scott J., Li, Linheng
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.06.2020
Nature Publishing Group
Subjects
1-Phosphatidylinositol 3-kinase
13/31
45
45/100
45/15
59
631/532/71
631/80/86
64
64/60
692/699/67/1059/2325
692/699/67/1059/2326
AKT protein
Animals
Antibiotics, Antineoplastic - pharmacology
Apoptosis
beta Catenin - physiology
Biomedical and Life Sciences
Cancer Research
Cancer therapies
Cell Biology
Cell Proliferation
Chemotherapy
Cytotoxicity
Developmental Biology
Doxorubicin
Doxorubicin - pharmacology
Drug Resistance, Neoplasm
Female
Gene expression
High-throughput screening
Humans
Immune checkpoint
Inhibitors
Leukemia
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - metabolism
Leukemia, Myeloid, Acute - pathology
Life Sciences
Male
Mice
Mice, Knockout
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
PD-L1 protein
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Progenitor cells
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
PTEN Phosphohydrolase - physiology
Stem cell transplantation
Stem Cells
Tumor Cells, Cultured
Tumorigenesis
Wnt protein
Wnt Proteins - physiology
Xenograft Model Antitumor Assays
β-Catenin
Online AccessGet full text

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Abstract Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape. Targeting resistant stem cells in leukaemia, Perry et al. show that doxorubicin at low doses decreases Akt-mediated β-catenin activity, downregulates expression of multiple immune-checkpoint genes and dampens tumorigenesis of leukaemia stem cells.
AbstractList Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-β-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.
Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-β-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-β-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.
Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.Targeting resistant stem cells in leukaemia, Perry et al. show that doxorubicin at low doses decreases Akt-mediated β-catenin activity, downregulates expression of multiple immune-checkpoint genes and dampens tumorigenesis of leukaemia stem cells.
Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape. Targeting resistant stem cells in leukaemia, Perry et al. show that doxorubicin at low doses decreases Akt-mediated β-catenin activity, downregulates expression of multiple immune-checkpoint genes and dampens tumorigenesis of leukaemia stem cells.
Author He, Xi C.
Schroeder, Kealan
Paulson, Ariel
Li, Linheng
Nemechek, Jacqelyn
Ruan, Linhao
Deshmukh, Prashant
Kasi, Rajeswari M.
Ryan, Robin
Yu, Xiazhen
Hembree, Mark
Roy, Anuradha
Weir, Scott J.
Broward, Melinda
Tao, Fang
Qian, Pengxu
Tran, Thanh-Huyen
Nguyen, Chi Thanh
Zhao, Meng
He, Zhiquan
August, Keith
Li, Zhenrui
Perry, John M.
Xu, Dong
Lu, Xiuling
Moran, Andrea
Guest, Erin
Sittampalam, G. Sitta
Godwin, Andrew
Venkatraman, Aparna
Lin, Tara
Ding, Sheng
Gamis, Alan S.
Pace, Jennifer
Dukes, Debra
Chen, Shiyuan
AuthorAffiliation 1 Stowers Institute for Medical Research, Kansas City, MO, USA
10 School of Pharmaceutical Science, Tsinghua University, Beijing, China
8 Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT, USA
11 Department of Cancer Biology, The Institute for Advancing Medical Innovation and University of Kansas Cancer Center, Kansas City, Kansas, USA
19 Present address: Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, US
13 Present address: Center for Cell Dynamics, Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
12 Department of Pathology and Laboratory Medicine and Division of Medical Oncology, Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
20 Present address: Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA
6 Department of Pharmaceutical Sciences, University of Connecti
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32313104$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1016/j.cell.2017.01.017
10.1093/bioinformatics/btu638
10.3109/10428194.2010.496505
10.1126/science.1150648
10.1182/blood-2011-04-345595
10.1016/j.stem.2014.02.006
10.1038/nm.2458
10.1038/nature06933
10.1016/j.stem.2010.11.014
10.1002/gene.10036
10.1016/j.cell.2019.03.025
10.1038/nm1253
10.1073/pnas.1018866109
10.1101/gad.17421911
10.1182/blood-2008-08-077941
10.1182/blood-2009-02-206722
10.1016/j.cell.2018.03.034
10.1021/bm5013822
10.1073/pnas.1100551108
10.1186/gb-2013-14-4-r36
10.1038/nature14404
10.1016/j.ccell.2017.04.010
10.1016/j.cell.2011.02.013
10.2174/092986711796011193
10.1093/emboj/18.21.5931
10.1038/nature10762
10.1111/bjh.13011
10.1016/j.stem.2012.09.001
10.1038/nrd4204
10.1038/leu.2017.87
10.1182/blood-2013-08-522698
10.1038/nature10738
10.1038/s41467-018-04313-6
10.1016/j.cell.2017.07.029
10.1038/s41598-017-08796-z
10.1038/nm.4439
10.1038/nature12634
10.1182/blood-2012-12-471904
10.1038/nm.2772
10.1186/s12943-016-0570-y
10.1158/2159-8290.CD-15-0283
10.1038/nrc.2017.117
10.1038/nm.2984
10.1084/jem.20050915
10.1002/0471142727.mb2129s109
10.1053/j.gastro.2010.05.037
10.1038/nm.2415
10.1371/journal.pbio.1000121
10.1126/science.1168988
10.1038/nrc2071
10.1038/nrc3599
10.1016/j.ccell.2015.10.012
10.1182/blood-2004-08-3037
10.1038/sj.onc.1210033
10.1016/j.jim.2009.06.008
10.3324/haematol.2009.011726
10.1038/ng1928
10.1182/blood-2016-09-740654
10.1093/bioinformatics/btp616
10.1182/blood-2012-01-401687
10.1158/0008-5472.CAN-12-4403
10.1038/nrc1819
10.1007/BF00173683
10.1158/0008-5472.CAN-14-1470
10.1038/leu.2008.83
10.1038/nature12113
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J.M.P. designed and conducted the primary experiments and wrote the manuscript. F.T. conducted ChIP-seq and ATAC-seq experiments. A.R. and G.S.S. conducted high-throughput screening. T.L. conducted the clinical trial. X.C.H., A.M. and D.D. conducted transplantation and drug treatments. X.L., R.M.K., T.-H.T., P.D. and C.T.N. designed and synthesized nanoDXR. S.J.W., E.G., K.A., A.S.G., R.R., and M.B. provided insights into clinical treatment. A.G. oversaw patient biospecimen acquisition. Z.H. and D.X. conducted computational simulation. S.D. provided β-catenin inhibitor. J.N., L.R., X.Y., J.P., K.S., M.Z., A.V., P.Q., Z.L. and M.H. helped in scientific discussion and facilitated some experiments. S.C. and A.P. conducted bioinformatics analysis. L.L. provided overall supervision of the project. All authors reviewed and approved the manuscript.
Author contributions
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References Freireich, Gehan, Rall, Schmidt, Skipper (CR65) 1966; 50
Xu (CR37) 2013; 73
Koren, Bentires-Alj (CR14) 2017; 31
Fruman, Rommel (CR29) 2014; 13
CR38
Ding (CR8) 2012; 481
Robinson, McCarthy, Smyth (CR68) 2010; 26
Bhatla (CR17) 2012; 119
Bolouri (CR18) 2018; 24
Casares (CR48) 2005; 202
He (CR26) 2007; 39
Wilson (CR56) 2010; 95
Greaves (CR6) 2007; 7
Huang (CR24) 2009; 119
Tran (CR64) 2014; 15
Roderick (CR33) 2014; 123
Zhou (CR30) 2017; 31
Schubbert (CR34) 2014; 74
Greaves, Maley (CR2) 2012; 481
Harada (CR62) 1999; 18
Al-Dhfyan, Alhoshani, Korashy (CR40) 2017; 16
Spranger, Bao, Gajewski (CR43) 2015; 523
Hsu (CR49) 2018; 9
Kikushige (CR58) 2010; 7
Griffiths (CR19) 2010; 51
Jinesh, Manyam, Mmeje, Baggerly, Kamat (CR51) 2017; 7
Hanahan, Weinberg (CR9) 2011; 144
Eguchi, Eguchi-Ishimae, Ishii (CR57) 2015; 56
Kreso, Dick (CR3) 2014; 14
Anders, Pyl, Huber (CR67) 2015; 31
Perry (CR27) 2011; 25
Knapp (CR28) 2017; 129
Chen, Tang, Zheng, Liu (CR52) 2009; 323
Castor (CR54) 2005; 11
Huang, Nguyen-McCarty, Hexner, Danet-Desnoyers, Klein (CR22) 2012; 18
Sharma, Hu-Lieskovan, Wargo, Ribas (CR42) 2017; 168
Lee (CR41) 2010; 139
Spranger, Gajewski (CR44) 2018; 18
Hu, Smyth (CR63) 2009; 347
Peng (CR11) 2016; 6
Kim (CR66) 2013; 14
Dick (CR4) 2008; 112
Kandoth (CR21) 2013; 502
Lechman (CR36) 2012; 11
Korkaya (CR23) 2009; 7
Hogan (CR16) 2011; 118
Eppert (CR5) 2011; 17
Guo (CR32) 2008; 453
Malta (CR50) 2018; 173
Kaveri (CR39) 2013; 122
Ciraolo, Morello, Hirsch (CR47) 2011; 18
Tenbaum (CR31) 2012; 18
Galluzzi, Buque, Kepp, Zitvogel, Kroemer (CR45) 2015; 28
Holohan, Van Schaeybroeck, Longley, Johnston (CR10) 2013; 13
Hong (CR53) 2008; 319
Fruman (CR12) 2017; 170
Gutierrez (CR15) 2009; 114
Cully, You, Levine, Mak (CR13) 2006; 6
Kuttesch (CR1) 1996; 14
Gothert (CR46) 2005; 105
Conley (CR25) 2012; 109
Huang, Chang, Fei, Wu, Chen (CR35) 2007; 26
Greaves (CR7) 2011; 17
Buenrostro, Wu, Chang, Greenleaf (CR69) 2015; 109
Dandekar (CR20) 2014; 167
Miao (CR60) 2019; 177
Jan (CR59) 2011; 108
Kong (CR55) 2008; 22
Lesche (CR61) 2002; 32
H Korkaya (507_CR23) 2009; 7
J Huang (507_CR24) 2009; 119
DJ Knapp (507_CR28) 2017; 129
L Galluzzi (507_CR45) 2015; 28
N Harada (507_CR62) 1999; 18
507_CR38
GY Chen (507_CR52) 2009; 323
TM Malta (507_CR50) 2018; 173
S Dandekar (507_CR20) 2014; 167
Y Kikushige (507_CR58) 2010; 7
P Sharma (507_CR42) 2017; 168
L Ding (507_CR8) 2012; 481
TH Tran (507_CR64) 2014; 15
S Anders (507_CR67) 2015; 31
W Huang (507_CR35) 2007; 26
M Greaves (507_CR2) 2012; 481
DA Fruman (507_CR29) 2014; 13
C Holohan (507_CR10) 2013; 13
A Kreso (507_CR3) 2014; 14
J Huang (507_CR22) 2012; 18
H Bolouri (507_CR18) 2018; 24
K Eppert (507_CR5) 2011; 17
D Hanahan (507_CR9) 2011; 144
E Ciraolo (507_CR47) 2011; 18
N Casares (507_CR48) 2005; 202
R Lesche (507_CR61) 2002; 32
D Kim (507_CR66) 2013; 14
LE Hogan (507_CR16) 2011; 118
K Wilson (507_CR56) 2010; 95
JM Hsu (507_CR49) 2018; 9
Y Hu (507_CR63) 2009; 347
SJ Conley (507_CR25) 2012; 109
JR Gothert (507_CR46) 2005; 105
JM Perry (507_CR27) 2011; 25
A Castor (507_CR54) 2005; 11
M Greaves (507_CR6) 2007; 7
DA Fruman (507_CR12) 2017; 170
S Spranger (507_CR44) 2018; 18
C Kandoth (507_CR21) 2013; 502
M Cully (507_CR13) 2006; 6
H Zhou (507_CR30) 2017; 31
JE Dick (507_CR4) 2008; 112
EJ Freireich (507_CR65) 1966; 50
A Al-Dhfyan (507_CR40) 2017; 16
G Lee (507_CR41) 2010; 139
M Jan (507_CR59) 2011; 108
S Spranger (507_CR43) 2015; 523
JF Kuttesch Jr. (507_CR1) 1996; 14
M Greaves (507_CR7) 2011; 17
W Peng (507_CR11) 2016; 6
S Koren (507_CR14) 2017; 31
JE Roderick (507_CR33) 2014; 123
GG Jinesh (507_CR51) 2017; 7
XC He (507_CR26) 2007; 39
JD Buenrostro (507_CR69) 2015; 109
EA Griffiths (507_CR19) 2010; 51
C Xu (507_CR37) 2013; 73
D Hong (507_CR53) 2008; 319
ER Lechman (507_CR36) 2012; 11
W Guo (507_CR32) 2008; 453
D Kaveri (507_CR39) 2013; 122
Y Miao (507_CR60) 2019; 177
Y Kong (507_CR55) 2008; 22
A Gutierrez (507_CR15) 2009; 114
MD Robinson (507_CR68) 2010; 26
M Eguchi (507_CR57) 2015; 56
S Schubbert (507_CR34) 2014; 74
T Bhatla (507_CR17) 2012; 119
SP Tenbaum (507_CR31) 2012; 18
References_xml – volume: 168
  start-page: 707
  year: 2017
  end-page: 723
  ident: CR42
  article-title: Primary, adaptive, and acquired resistance to cancer immunotherapy
  publication-title: Cell
  doi: 10.1016/j.cell.2017.01.017
– volume: 31
  start-page: 166
  year: 2015
  end-page: 169
  ident: CR67
  article-title: HTSeq—a Python framework to work with high-throughput sequencing data
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btu638
– volume: 51
  start-page: 1711
  year: 2010
  end-page: 1719
  ident: CR19
  article-title: Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter hypermethylation
  publication-title: Leuk. Lymphoma
  doi: 10.3109/10428194.2010.496505
– volume: 319
  start-page: 336
  year: 2008
  end-page: 339
  ident: CR53
  article-title: Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia
  publication-title: Science
  doi: 10.1126/science.1150648
– volume: 118
  start-page: 5218
  year: 2011
  end-page: 5226
  ident: CR16
  article-title: Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies
  publication-title: Blood
  doi: 10.1182/blood-2011-04-345595
– volume: 14
  start-page: 275
  year: 2014
  end-page: 291
  ident: CR3
  article-title: Evolution of the cancer stem cell model
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2014.02.006
– volume: 17
  start-page: 1046
  year: 2011
  end-page: 1048
  ident: CR7
  article-title: Cancer stem cells renew their impact
  publication-title: Nat. Med.
  doi: 10.1038/nm.2458
– volume: 453
  start-page: 529
  year: 2008
  end-page: 533
  ident: CR32
  article-title: Multi-genetic events collaboratively contribute to -null leukaemia stem-cell formation
  publication-title: Nature
  doi: 10.1038/nature06933
– volume: 7
  start-page: 708
  year: 2010
  end-page: 717
  ident: CR58
  article-title: TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2010.11.014
– volume: 32
  start-page: 148
  year: 2002
  end-page: 149
  ident: CR61
  article-title: Cre/ -mediated inactivation of the murine tumor suppressor gene
  publication-title: Genesis
  doi: 10.1002/gene.10036
– volume: 177
  start-page: 1172
  year: 2019
  end-page: 1186
  ident: CR60
  article-title: Adaptive immune resistance emerges from tumor-initiating stem cells
  publication-title: Cell
  doi: 10.1016/j.cell.2019.03.025
– volume: 11
  start-page: 630
  year: 2005
  end-page: 637
  ident: CR54
  article-title: Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
  publication-title: Nat. Med.
  doi: 10.1038/nm1253
– volume: 109
  start-page: 2784
  year: 2012
  end-page: 2789
  ident: CR25
  article-title: Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia
  publication-title: Proc. Natl Acad. Sci. USA
  doi: 10.1073/pnas.1018866109
– volume: 25
  start-page: 1928
  year: 2011
  end-page: 1942
  ident: CR27
  article-title: Cooperation between both Wnt/β-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion
  publication-title: Genes Dev.
  doi: 10.1101/gad.17421911
– volume: 112
  start-page: 4793
  year: 2008
  end-page: 4807
  ident: CR4
  article-title: Stem cell concepts renew cancer research
  publication-title: Blood
  doi: 10.1182/blood-2008-08-077941
– volume: 114
  start-page: 647
  year: 2009
  end-page: 650
  ident: CR15
  article-title: High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia
  publication-title: Blood
  doi: 10.1182/blood-2009-02-206722
– volume: 173
  start-page: 338
  year: 2018
  end-page: 354 e315
  ident: CR50
  article-title: Machine learning identifies stemness features associated with oncogenic dedifferentiation
  publication-title: Cell
  doi: 10.1016/j.cell.2018.03.034
– volume: 15
  start-page: 4363
  year: 2014
  end-page: 4375
  ident: CR64
  article-title: Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors
  publication-title: Biomacromolecules
  doi: 10.1021/bm5013822
– volume: 108
  start-page: 5009
  year: 2011
  end-page: 5014
  ident: CR59
  article-title: Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker
  publication-title: Proc. Natl Acad. Sci. USA
  doi: 10.1073/pnas.1100551108
– volume: 14
  year: 2013
  ident: CR66
  article-title: TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions
  publication-title: Genome Biol.
  doi: 10.1186/gb-2013-14-4-r36
– volume: 523
  start-page: 231
  year: 2015
  end-page: 235
  ident: CR43
  article-title: Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
  publication-title: Nature
  doi: 10.1038/nature14404
– volume: 31
  start-page: 616
  year: 2017
  end-page: 618
  ident: CR14
  article-title: Tackling resistance to PI3K inhibition by targeting the epigenome
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2017.04.010
– volume: 144
  start-page: 646
  year: 2011
  end-page: 674
  ident: CR9
  article-title: Hallmarks of cancer: the next generation
  publication-title: Cell.
  doi: 10.1016/j.cell.2011.02.013
– volume: 18
  start-page: 2674
  year: 2011
  end-page: 2685
  ident: CR47
  article-title: Present and future of PI3K pathway inhibition in cancer: perspectives and limitations
  publication-title: Curr. Med. Chem.
  doi: 10.2174/092986711796011193
– volume: 56
  start-page: 1871
  year: 2015
  end-page: 1881
  ident: CR57
  article-title: Recent progress in leukemic stem cell research for childhood leukemia
  publication-title: Rinsho Ketsueki
– volume: 18
  start-page: 5931
  year: 1999
  end-page: 5942
  ident: CR62
  article-title: Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene
  publication-title: EMBO J.
  doi: 10.1093/emboj/18.21.5931
– volume: 481
  start-page: 306
  year: 2012
  end-page: 313
  ident: CR2
  article-title: Clonal evolution in cancer
  publication-title: Nature
  doi: 10.1038/nature10762
– volume: 167
  start-page: 87
  year: 2014
  end-page: 99
  ident: CR20
  article-title: Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia
  publication-title: Br. J. Haematol.
  doi: 10.1111/bjh.13011
– volume: 11
  start-page: 799
  year: 2012
  end-page: 811
  ident: CR36
  article-title: Attenuation of miR-126 activity expands HSC in vivo without exhaustion
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2012.09.001
– volume: 13
  start-page: 140
  year: 2014
  end-page: 156
  ident: CR29
  article-title: PI3K and cancer: lessons, challenges and opportunities
  publication-title: Nat. Rev. Drug Discovery
  doi: 10.1038/nrd4204
– volume: 31
  start-page: 2065
  year: 2017
  end-page: 2074
  ident: CR30
  article-title: Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo
  publication-title: Leukemia
  doi: 10.1038/leu.2017.87
– volume: 123
  start-page: 1040
  year: 2014
  end-page: 1050
  ident: CR33
  article-title: c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells
  publication-title: Blood
  doi: 10.1182/blood-2013-08-522698
– volume: 481
  start-page: 506
  year: 2012
  end-page: 510
  ident: CR8
  article-title: Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
  publication-title: Nature
  doi: 10.1038/nature10738
– volume: 9
  year: 2018
  ident: CR49
  article-title: STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-018-04313-6
– volume: 170
  start-page: 605
  year: 2017
  end-page: 635
  ident: CR12
  article-title: The PI3K pathway in human disease
  publication-title: Cell
  doi: 10.1016/j.cell.2017.07.029
– volume: 7
  year: 2017
  ident: CR51
  article-title: Surface PD-L1, E-cadherin, CD24, and VEGFR2 as markers of epithelial cancer stem cells associated with rapid tumorigenesis
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-017-08796-z
– volume: 24
  start-page: 103
  year: 2018
  end-page: 112
  ident: CR18
  article-title: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions
  publication-title: Nat. Med.
  doi: 10.1038/nm.4439
– volume: 502
  start-page: 333
  year: 2013
  end-page: 339
  ident: CR21
  article-title: Mutational landscape and significance across 12 major cancer types
  publication-title: Nature
  doi: 10.1038/nature12634
– volume: 122
  start-page: 694
  year: 2013
  end-page: 704
  ident: CR39
  article-title: β-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL
  publication-title: Blood
  doi: 10.1182/blood-2012-12-471904
– volume: 18
  start-page: 892
  year: 2012
  end-page: 901
  ident: CR31
  article-title: β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer
  publication-title: Nat. Med.
  doi: 10.1038/nm.2772
– volume: 16
  year: 2017
  ident: CR40
  article-title: Aryl hydrocarbon receptor/cytochrome P450 1A1 pathway mediates breast cancer stem cells expansion through PTEN inhibition and β-Catenin and Akt activation
  publication-title: Mol. Cancer
  doi: 10.1186/s12943-016-0570-y
– volume: 6
  start-page: 202
  year: 2016
  end-page: 216
  ident: CR11
  article-title: Loss of PTEN promotes resistance to T cell-mediated immunotherapy
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-15-0283
– volume: 18
  start-page: 139
  year: 2018
  end-page: 147
  ident: CR44
  article-title: Impact of oncogenic pathways on evasion of antitumour immune responses
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc.2017.117
– volume: 18
  start-page: 1778
  year: 2012
  end-page: 1785
  ident: CR22
  article-title: Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways
  publication-title: Nat. Med.
  doi: 10.1038/nm.2984
– volume: 202
  start-page: 1691
  year: 2005
  end-page: 1701
  ident: CR48
  article-title: Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death
  publication-title: J. Exp. Med.
  doi: 10.1084/jem.20050915
– volume: 109
  start-page: 21
  year: 2015
  end-page: 29
  ident: CR69
  article-title: ATAC-seq: A method for assaying chromatin accessibility genome-wide
  publication-title: Curr. Protoc. Mol. Biol.
  doi: 10.1002/0471142727.mb2129s109
– volume: 139
  start-page: 869
  year: 2010
  end-page: 881
  ident: CR41
  article-title: Phosphoinositide 3-kinase signaling mediates β-catenin activation in intestinal epithelial stem and progenitor cells in colitis
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2010.05.037
– volume: 17
  start-page: 1086
  year: 2011
  end-page: 1093
  ident: CR5
  article-title: Stem cell gene expression programs influence clinical outcome in human leukemia
  publication-title: Nat. Med.
  doi: 10.1038/nm.2415
– volume: 7
  start-page: e1000121
  year: 2009
  ident: CR23
  article-title: Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling
  publication-title: PLoS Biol.
  doi: 10.1371/journal.pbio.1000121
– volume: 50
  start-page: 219
  year: 1966
  end-page: 244
  ident: CR65
  article-title: Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man
  publication-title: Cancer Chemother. Rep.
– volume: 119
  start-page: 3519
  year: 2009
  end-page: 3529
  ident: CR24
  article-title: Pivotal role for glycogen synthase kinase-3 in hematopoietic stem cell homeostasis in mice
  publication-title: J. Clin. Invest.
– volume: 323
  start-page: 1722
  year: 2009
  end-page: 1725
  ident: CR52
  article-title: CD24 and Siglec-10 selectively repress tissue damage-induced immune responses
  publication-title: Science
  doi: 10.1126/science.1168988
– volume: 7
  start-page: 213
  year: 2007
  end-page: 221
  ident: CR6
  article-title: Darwinian medicine: a case for cancer
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc2071
– volume: 13
  start-page: 714
  year: 2013
  end-page: 726
  ident: CR10
  article-title: Cancer drug resistance: an evolving paradigm
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc3599
– volume: 28
  start-page: 690
  year: 2015
  end-page: 714
  ident: CR45
  article-title: Immunological effects of conventional chemotherapy and targeted anticancer agents
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2015.10.012
– volume: 105
  start-page: 2724
  year: 2005
  end-page: 2732
  ident: CR46
  article-title: In vivo fate-tracing studies using the stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis
  publication-title: Blood
  doi: 10.1182/blood-2004-08-3037
– volume: 26
  start-page: 2471
  year: 2007
  end-page: 2482
  ident: CR35
  article-title: GSK3β mediates suppression of cyclin D2 expression by tumor suppressor PTEN
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1210033
– ident: CR38
– volume: 347
  start-page: 70
  year: 2009
  end-page: 78
  ident: CR63
  article-title: ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays
  publication-title: J. Immunol. Methods
  doi: 10.1016/j.jim.2009.06.008
– volume: 95
  start-page: 679
  year: 2010
  end-page: 683
  ident: CR56
  article-title: Flow minimal residual disease monitoring of candidate leukemic stem cells defined by the immunophenotype, CD34 CD38 CD19 in B-lineage childhood acute lymphoblastic leukemia
  publication-title: Haematologica
  doi: 10.3324/haematol.2009.011726
– volume: 39
  start-page: 189
  year: 2007
  end-page: 198
  ident: CR26
  article-title: PTEN-deficient intestinal stem cells initiate intestinal polyposis
  publication-title: Nat. Genet.
  doi: 10.1038/ng1928
– volume: 129
  start-page: 307
  year: 2017
  end-page: 318
  ident: CR28
  article-title: Distinct signaling programs control human hematopoietic stem cell survival and proliferation
  publication-title: Blood
  doi: 10.1182/blood-2016-09-740654
– volume: 26
  start-page: 139
  year: 2010
  end-page: 140
  ident: CR68
  article-title: edgeR: a Bioconductor package for differential expression analysis of digital gene expression data
  publication-title: Bioinformatics.
  doi: 10.1093/bioinformatics/btp616
– volume: 119
  start-page: 5201
  year: 2012
  end-page: 5210
  ident: CR17
  article-title: Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia
  publication-title: Blood
  doi: 10.1182/blood-2012-01-401687
– volume: 73
  start-page: 3181
  year: 2013
  end-page: 3189
  ident: CR37
  article-title: beta-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-12-4403
– volume: 6
  start-page: 184
  year: 2006
  end-page: 192
  ident: CR13
  article-title: Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc1819
– volume: 14
  start-page: 55
  year: 1996
  end-page: 67
  ident: CR1
  article-title: Multidrug resistance in pediatric oncology
  publication-title: Invest. New Drugs
  doi: 10.1007/BF00173683
– volume: 74
  start-page: 7048
  year: 2014
  end-page: 7059
  ident: CR34
  article-title: Targeting the MYC and PI3K pathways eliminates leukemia-initiating cells in T-cell acute lymphoblastic leukemia
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-14-1470
– volume: 22
  start-page: 1207
  year: 2008
  end-page: 1213
  ident: CR55
  article-title: CD34 CD38 CD19 as well as CD34 CD38 CD19 cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL
  publication-title: Leukemia
  doi: 10.1038/leu.2008.83
– volume: 95
  start-page: 679
  year: 2010
  ident: 507_CR56
  publication-title: Haematologica
  doi: 10.3324/haematol.2009.011726
– volume: 108
  start-page: 5009
  year: 2011
  ident: 507_CR59
  publication-title: Proc. Natl Acad. Sci. USA
  doi: 10.1073/pnas.1100551108
– volume: 31
  start-page: 2065
  year: 2017
  ident: 507_CR30
  publication-title: Leukemia
  doi: 10.1038/leu.2017.87
– volume: 7
  start-page: 213
  year: 2007
  ident: 507_CR6
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc2071
– volume: 167
  start-page: 87
  year: 2014
  ident: 507_CR20
  publication-title: Br. J. Haematol.
  doi: 10.1111/bjh.13011
– volume: 18
  start-page: 892
  year: 2012
  ident: 507_CR31
  publication-title: Nat. Med.
  doi: 10.1038/nm.2772
– volume: 26
  start-page: 2471
  year: 2007
  ident: 507_CR35
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1210033
– volume: 323
  start-page: 1722
  year: 2009
  ident: 507_CR52
  publication-title: Science
  doi: 10.1126/science.1168988
– volume: 347
  start-page: 70
  year: 2009
  ident: 507_CR63
  publication-title: J. Immunol. Methods
  doi: 10.1016/j.jim.2009.06.008
– volume: 50
  start-page: 219
  year: 1966
  ident: 507_CR65
  publication-title: Cancer Chemother. Rep.
– volume: 31
  start-page: 166
  year: 2015
  ident: 507_CR67
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btu638
– volume: 502
  start-page: 333
  year: 2013
  ident: 507_CR21
  publication-title: Nature
  doi: 10.1038/nature12634
– volume: 119
  start-page: 5201
  year: 2012
  ident: 507_CR17
  publication-title: Blood
  doi: 10.1182/blood-2012-01-401687
– volume: 24
  start-page: 103
  year: 2018
  ident: 507_CR18
  publication-title: Nat. Med.
  doi: 10.1038/nm.4439
– volume: 28
  start-page: 690
  year: 2015
  ident: 507_CR45
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2015.10.012
– volume: 105
  start-page: 2724
  year: 2005
  ident: 507_CR46
  publication-title: Blood
  doi: 10.1182/blood-2004-08-3037
– volume: 17
  start-page: 1046
  year: 2011
  ident: 507_CR7
  publication-title: Nat. Med.
  doi: 10.1038/nm.2458
– volume: 73
  start-page: 3181
  year: 2013
  ident: 507_CR37
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-12-4403
– volume: 16
  year: 2017
  ident: 507_CR40
  publication-title: Mol. Cancer
  doi: 10.1186/s12943-016-0570-y
– volume: 14
  start-page: 55
  year: 1996
  ident: 507_CR1
  publication-title: Invest. New Drugs
  doi: 10.1007/BF00173683
– volume: 114
  start-page: 647
  year: 2009
  ident: 507_CR15
  publication-title: Blood
  doi: 10.1182/blood-2009-02-206722
– volume: 51
  start-page: 1711
  year: 2010
  ident: 507_CR19
  publication-title: Leuk. Lymphoma
  doi: 10.3109/10428194.2010.496505
– volume: 144
  start-page: 646
  year: 2011
  ident: 507_CR9
  publication-title: Cell.
  doi: 10.1016/j.cell.2011.02.013
– volume: 109
  start-page: 21
  year: 2015
  ident: 507_CR69
  publication-title: Curr. Protoc. Mol. Biol.
  doi: 10.1002/0471142727.mb2129s109
– volume: 39
  start-page: 189
  year: 2007
  ident: 507_CR26
  publication-title: Nat. Genet.
  doi: 10.1038/ng1928
– volume: 18
  start-page: 2674
  year: 2011
  ident: 507_CR47
  publication-title: Curr. Med. Chem.
  doi: 10.2174/092986711796011193
– ident: 507_CR38
  doi: 10.1038/nature12113
– volume: 15
  start-page: 4363
  year: 2014
  ident: 507_CR64
  publication-title: Biomacromolecules
  doi: 10.1021/bm5013822
– volume: 168
  start-page: 707
  year: 2017
  ident: 507_CR42
  publication-title: Cell
  doi: 10.1016/j.cell.2017.01.017
– volume: 129
  start-page: 307
  year: 2017
  ident: 507_CR28
  publication-title: Blood
  doi: 10.1182/blood-2016-09-740654
– volume: 56
  start-page: 1871
  year: 2015
  ident: 507_CR57
  publication-title: Rinsho Ketsueki
– volume: 123
  start-page: 1040
  year: 2014
  ident: 507_CR33
  publication-title: Blood
  doi: 10.1182/blood-2013-08-522698
– volume: 523
  start-page: 231
  year: 2015
  ident: 507_CR43
  publication-title: Nature
  doi: 10.1038/nature14404
– volume: 22
  start-page: 1207
  year: 2008
  ident: 507_CR55
  publication-title: Leukemia
  doi: 10.1038/leu.2008.83
– volume: 170
  start-page: 605
  year: 2017
  ident: 507_CR12
  publication-title: Cell
  doi: 10.1016/j.cell.2017.07.029
– volume: 319
  start-page: 336
  year: 2008
  ident: 507_CR53
  publication-title: Science
  doi: 10.1126/science.1150648
– volume: 119
  start-page: 3519
  year: 2009
  ident: 507_CR24
  publication-title: J. Clin. Invest.
– volume: 31
  start-page: 616
  year: 2017
  ident: 507_CR14
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2017.04.010
– volume: 11
  start-page: 630
  year: 2005
  ident: 507_CR54
  publication-title: Nat. Med.
  doi: 10.1038/nm1253
– volume: 32
  start-page: 148
  year: 2002
  ident: 507_CR61
  publication-title: Genesis
  doi: 10.1002/gene.10036
– volume: 481
  start-page: 506
  year: 2012
  ident: 507_CR8
  publication-title: Nature
  doi: 10.1038/nature10738
– volume: 7
  year: 2017
  ident: 507_CR51
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-017-08796-z
– volume: 13
  start-page: 714
  year: 2013
  ident: 507_CR10
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc3599
– volume: 18
  start-page: 5931
  year: 1999
  ident: 507_CR62
  publication-title: EMBO J.
  doi: 10.1093/emboj/18.21.5931
– volume: 14
  year: 2013
  ident: 507_CR66
  publication-title: Genome Biol.
  doi: 10.1186/gb-2013-14-4-r36
– volume: 9
  year: 2018
  ident: 507_CR49
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-018-04313-6
– volume: 481
  start-page: 306
  year: 2012
  ident: 507_CR2
  publication-title: Nature
  doi: 10.1038/nature10762
– volume: 17
  start-page: 1086
  year: 2011
  ident: 507_CR5
  publication-title: Nat. Med.
  doi: 10.1038/nm.2415
– volume: 14
  start-page: 275
  year: 2014
  ident: 507_CR3
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2014.02.006
– volume: 74
  start-page: 7048
  year: 2014
  ident: 507_CR34
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-14-1470
– volume: 7
  start-page: e1000121
  year: 2009
  ident: 507_CR23
  publication-title: PLoS Biol.
  doi: 10.1371/journal.pbio.1000121
– volume: 139
  start-page: 869
  year: 2010
  ident: 507_CR41
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2010.05.037
– volume: 13
  start-page: 140
  year: 2014
  ident: 507_CR29
  publication-title: Nat. Rev. Drug Discovery
  doi: 10.1038/nrd4204
– volume: 25
  start-page: 1928
  year: 2011
  ident: 507_CR27
  publication-title: Genes Dev.
  doi: 10.1101/gad.17421911
– volume: 177
  start-page: 1172
  year: 2019
  ident: 507_CR60
  publication-title: Cell
  doi: 10.1016/j.cell.2019.03.025
– volume: 112
  start-page: 4793
  year: 2008
  ident: 507_CR4
  publication-title: Blood
  doi: 10.1182/blood-2008-08-077941
– volume: 118
  start-page: 5218
  year: 2011
  ident: 507_CR16
  publication-title: Blood
  doi: 10.1182/blood-2011-04-345595
– volume: 18
  start-page: 139
  year: 2018
  ident: 507_CR44
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc.2017.117
– volume: 202
  start-page: 1691
  year: 2005
  ident: 507_CR48
  publication-title: J. Exp. Med.
  doi: 10.1084/jem.20050915
– volume: 109
  start-page: 2784
  year: 2012
  ident: 507_CR25
  publication-title: Proc. Natl Acad. Sci. USA
  doi: 10.1073/pnas.1018866109
– volume: 18
  start-page: 1778
  year: 2012
  ident: 507_CR22
  publication-title: Nat. Med.
  doi: 10.1038/nm.2984
– volume: 173
  start-page: 338
  year: 2018
  ident: 507_CR50
  publication-title: Cell
  doi: 10.1016/j.cell.2018.03.034
– volume: 6
  start-page: 184
  year: 2006
  ident: 507_CR13
  publication-title: Nat. Rev. Cancer
  doi: 10.1038/nrc1819
– volume: 122
  start-page: 694
  year: 2013
  ident: 507_CR39
  publication-title: Blood
  doi: 10.1182/blood-2012-12-471904
– volume: 26
  start-page: 139
  year: 2010
  ident: 507_CR68
  publication-title: Bioinformatics.
  doi: 10.1093/bioinformatics/btp616
– volume: 11
  start-page: 799
  year: 2012
  ident: 507_CR36
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2012.09.001
– volume: 453
  start-page: 529
  year: 2008
  ident: 507_CR32
  publication-title: Nature
  doi: 10.1038/nature06933
– volume: 7
  start-page: 708
  year: 2010
  ident: 507_CR58
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2010.11.014
– volume: 6
  start-page: 202
  year: 2016
  ident: 507_CR11
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-15-0283
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Snippet Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate...
Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-β-catenin and PI3K-Akt pathways cooperate...
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StartPage 689
SubjectTerms 1-Phosphatidylinositol 3-kinase
13/31
45
45/100
45/15
59
631/532/71
631/80/86
64
64/60
692/699/67/1059/2325
692/699/67/1059/2326
AKT protein
Animals
Antibiotics, Antineoplastic - pharmacology
Apoptosis
beta Catenin - physiology
Biomedical and Life Sciences
Cancer Research
Cancer therapies
Cell Biology
Cell Proliferation
Chemotherapy
Cytotoxicity
Developmental Biology
Doxorubicin
Doxorubicin - pharmacology
Drug Resistance, Neoplasm
Female
Gene expression
High-throughput screening
Humans
Immune checkpoint
Inhibitors
Leukemia
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - metabolism
Leukemia, Myeloid, Acute - pathology
Life Sciences
Male
Mice
Mice, Knockout
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
PD-L1 protein
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Progenitor cells
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
PTEN Phosphohydrolase - physiology
Stem cell transplantation
Stem Cells
Tumor Cells, Cultured
Tumorigenesis
Wnt protein
Wnt Proteins - physiology
Xenograft Model Antitumor Assays
β-Catenin
Title Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells
URI https://link.springer.com/article/10.1038/s41556-020-0507-y
https://www.ncbi.nlm.nih.gov/pubmed/32313104
https://www.proquest.com/docview/2410668400
https://www.proquest.com/docview/2393037881
https://pubmed.ncbi.nlm.nih.gov/PMC8010717
Volume 22
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