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

•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...

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Veröffentlicht in:	Blood 2022-11, Vol.140 (20), p.2127-2141
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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
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