Multiple BCL2 mutations cooccurring with Gly101Val emerge in chronic lymphocytic leukemia progression on venetoclax

Author:

Blombery Piers123,Thompson Ella R.13,Nguyen Tamia1,Birkinshaw Richard W.34ORCID,Gong Jia-nan34,Chen Xiangting1,McBean Michelle1,Thijssen Rachel34,Conway Thomas1ORCID,Anderson Mary Ann234,Seymour John F.23ORCID,Westerman David A.123,Czabotar Peter E.34ORCID,Huang David C. S.34ORCID,Roberts Andrew W.234ORCID

Affiliation:

1. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;

2. Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, VIC, Australia;

3. University of Melbourne, Melbourne, VIC, Australia; and

4. The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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