Acquired BCL2 variants associated with venetoclax resistance in acute myeloid leukemia

Fiona C Brown; Xin Wang; Richard W Birkinshaw; Chong Chyn Chua; Thomas David Morley; Sila Kasapgil; Giovanna Pomilio; Piers Blombery; David Ching Siang Huang Professor; Peter E Czabotar; Salvatore F Priore; Guang Yang; Martin P Carroll; Andrew H Wei; Alexander E Perl

doi:10.1182/bloodadvances.2024014446

Acquired BCL2 variants associated with venetoclax resistance in acute myeloid leukemia

Blood Adv. 2024 Oct 7:bloodadvances.2024014446. doi: 10.1182/bloodadvances.2024014446. Online ahead of print.

Authors

Affiliations

¹ Walter and Eliza Hall Institute of Medical Research, Australia.
² Memorial Sloan Kettering Cancer Center, New York, New York, United States.
³ The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
⁴ Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
⁵ Peter MacCallum Cancer Centre, Melbourne, Australia.
⁶ The Walter & Eliza Hall Institute of Medical Research, Parkville, Australia.
⁷ Division of Precision and Computational Diagnostics, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA, Philadelphia, Pennsylvania, United States.
⁸ Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
⁹ University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States.
¹⁰ Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

PMID: 39374584
DOI: 10.1182/bloodadvances.2024014446

Abstract

We report and characterize three venetoclax-resistant BCL2 variants arising during venetoclax/azacitidine therapy in acute myeloid leukemia (AML). Our results indicate the potential for on-target venetoclax resistance in patients with AML at relapse.