TY - JOUR
T1 - Expression of BCL2 alternative proteins and association with outcome in CLL patients treated with venetoclax
AU - Marques-Piubelli, Mario L.
AU - Schlette, Ellen J.
AU - Khoury, Joseph D.
AU - Furqan, Fateeha
AU - Vega, Francisco
AU - Soto, Luisa M.Solis
AU - Wistuba, Ignacio I.
AU - Wierda, William G.
AU - Konopleva, Marina
AU - Ferrajoli, Alessandra
AU - Strati, Paolo
N1 - Funding Information:
The study was partially supported by MD Anderson Cancer Center Support grant CA016672.
Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - apoptosis
KW - BCL-2
KW - BCL-2 family
KW - Chronic lymphocytic leukemia
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U2 - 10.1080/10428194.2020.1861278
DO - 10.1080/10428194.2020.1861278
M3 - Article
C2 - 33327833
AN - SCOPUS:85097613329
SN - 1042-8194
VL - 62
SP - 1129
EP - 1135
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 5
ER -