Multiple BCL2 mutations cooccurring with Gly101Val emerge in chronic lymphocytic leukemia progression on venetoclax
Piers Blombery, Ella R Thompson, Nguyen Tamia, Richard W Birkinshaw, Jia-Nan Gong, Xiangting Chen, Michelle McBean, Rachel Thijssen, Thomas Conway, Mary Ann Anderson, John F Seymour, David A Westerman, Peter E Czabotar, David CS Huang, Andrew W Roberts
BLOOD | AMER SOC HEMATOLOGY | Published : 2020
The BCL2 inhibitor venetoclax has complete response rates of up to 50% in chronic lymphocytic leukemia patients, but secondary resistance reflecting acquired mutations in BCL2 can lead to treatment failure. Blombery et al report that an unexpectedly large number of patients carry multiple BCL2 mutations with subclonal variation in their occurrence.
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Awarded by Leukemia and Lymphoma Society
Awarded by National Health and Medical Research Council of Australia
This research was supported by grants from the Snowdome Foundation (P.B. and M.A.A.), Vision Super and the Wilson Centre for Lymphoma Genomics (P.B. and D.A.W.), the Leukemia and Lymphoma Society (fellowship 5467-18 [R.T.], SCOR 7015-18 [D.C.S.H. and A.W.R.]), the National Health and Medical Research Council of Australia (fellowships 1079700 [P.E.C.], 1043149 [D.C.S.H], and 1079560 [A.W.R.]), and grants to project 1141874 (P.E.C.), program 1113133 (D.C.S.H.), and program 1113577 (A.W.R.). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme.