Expression of BCL2 alternative proteins and association with outcome in CLL patients treated with venetoclax

Mario L. Marques-Piubelli, Ellen J. Schlette, Joseph D. Khoury, Fateeha Furqan, Francisco Vega, Luisa M.Solis Soto, Ignacio I. Wistuba, William G. Wierda, Marina Konopleva, Alessandra Ferrajoli, Paolo Strati

Research output: Contribution to journalArticlepeer-review

Abstract

Venetoclax, a BCL-2 inhibitor, is highly effective for the treatment of patients with chronic lymphocytic leukemia (CLL) and dependence on alternative proteins may result in resistance to BCL-2 inhibition. Patients with CLL treated with venetoclax as monotherapy at MD Anderson Cancer Center between 05/2012 and 01/2016 were included and pretreatment bone marrow was analyzed by immunohistochemistry (IHC) for BCL-W, BCL-XL, BCL2-A1 and MCL-1. Twenty-seven patients were included. BCL-W + and BCL-2A1+ was found in 15% and 7% of the patients, respectively. Both BCL-XL and MCL-1 were negative in all samples. A higher CR and longer PFS rates were observed in patients with BCL-W+ (p =.60, p =.46), BCL-2A1+ (p =.60, p =.29), and either BCL-W + or BCL-2A1+ (p =.33, p =.20), though not statistically significant. Pretreatment IHC expression of BCL-2 alternative proteins does not predict response to venetoclax in CLL, but may be a surrogate for an indolent biology. Sensitive techniques are needed to explore anti-apoptotic pathways.

Original languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - 2020
Externally publishedYes

Keywords

  • BCL-2
  • BCL-2 family
  • Chronic lymphocytic leukemia
  • apoptosis

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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