High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy

Abstract

The BCL-2 proto-oncogene encodes a mitochondrial protein that blocks programmed cell death. High amounts of bcl-2 protein are found not only in lymphoid malignancies, but also in normal tissues characterized by apoptotic cell death, including bone marrow. Using a monoclonal antibody to bcl-2 protein, we analyzed 82 samples of newly diagnosed acute myeloid leukemia. The number of bcl-2+ cells in each sample was heterogeneous (range, 0% to 95%), with a mean of 23%. The percentage of bcl-2+ cells was higher in M4 and M5 types, according to French- American-British classification, and in cases with high white blood cell counts. bcl-2 expression was also correlated with that of the stem cell marker CD34. In vitro survival of leukemic cells maintained in liquid culture in the absence of growth factors was significantly longer in cases with a high percentage of bcl-2+ cells. High expression of bcl-2 was associated with a low complete remission rate after intensive chemotherapy (29% in cases with 20% or more positive cells v 85% in cases with less than 20% positive cells, P < 10(-5)) and with a significantly shorter survival. In multivariate analysis, the percentage of bcl-2+ cells (or the blast survival in culture), age, and the percentage of CD34+ cells were independently associated with poor survival.

Structure–Activity Relationships and Molecular Docking Analysis of Mcl-1 Targeting Renieramycin T Analogues in Patient-derived Lung Cancer Cells

“…The protein levels of Bcl-2 and Mcl-1 in various types of tumor tissues were found to be frequently augmented at a higher ratio than the other anti-apoptotic proteins in the Bcl-2 family [26]. In particular, increased expressions of Bcl-2 and Mcl-1 reflect a poor prognosis for many malignancies, including lung cancer [37][38][39]. Not only is their increased expression critical for oncogenesis and cancer progression, but these proteins are also involved in conferring chemotherapeutic drug resistance [35,[40][41][42][43].…”

Co-Operativity between MYC and BCL-2 Pro-Survival Proteins in Cancer

“…For example, enhanced expression of BCL-2 is associated with the development of androgen-refractory prostate cancer [40], whilst in CLL, higher expression of BCL-2 is an adverse prognostic feature [41]. High BCL-2 expression also dictates poorer patient outcome following standard chemotherapy [22,39,[42][43][44]. However, it should be noted that the role of BCL-2 expression as a prognostic marker also does not always hold up [35,45,46] such as in studies of advanced head and neck carcinoma and bladder cancer [47,48].…”

Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia

“…Pathogenesis of AML involves overexpression of the anti-apoptotic protein B-cell lymphoma 2 (BCL2), which promotes proliferation of lymphocytes. Increased BCL2 production is linked to high mortality rates in AML patients and poor responsiveness to chemotherapy [96][97][98]. As such, DiNardo et al (2020) investigated a drug therapy combination of azacitidine and venetoclax, a BCL2 inhibitor, in a phase 3, multicenter, randomized, double-blind, placebo-controlled trial [99].…”