Single-cell multiomics reveal the scale of multilayered adaptations enabling CLL relapse during venetoclax therapy

• Published in: Blood Vol. 140; no. 20; pp. 2127 - 2141
• Main Authors: Thijssen, Rachel, Tian, Luyi, Anderson, Mary Ann, Flensburg, Christoffer, Jarratt, Andrew, Garnham, Alexandra L., Jabbari, Jafar S., Peng, Hongke, Lew, Thomas E., Teh, Charis E., Gouil, Quentin, Georgiou, Angela, Tan, Tania, Djajawi, Tirta M., Tam, Constantine S., Seymour, John F., Blombery, Piers, Gray, Daniel H.D., Majewski, Ian J., Ritchie, Matthew E., Roberts, Andrew W., Huang, David C.S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.11.2022
• Subjects: Antineoplastic Agents - therapeutic use; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; Drug Resistance, Neoplasm - genetics; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; NF-kappa B; Proto-Oncogene Proteins c-bcl-2 - metabolism; Recurrence

•Multiple independent but recurring genetic and epigenetic changes drive venetoclax resistance, with marked NF-κB activation ubiquitous.•NF-κB activation is apparent within the first year of therapy, and most changes in CLL cells are sustained by ongoing venetoclax therapy. [Display omitted] Venetoc...