Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?

Bibi Kulsoom,1 Tahir Sultan Shamsi,1 Nasir Ali Afsar,2,3 Zahida Memon,4 Nikhat Ahmed,4 Syed Nazrul Hasnain5 1National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan; 2Jinnah Medical and Dental College, Karachi, Pakistan; 3College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 4Ziauddin University, Karachi, Pakistan; 5Dow International Medical College, Karachi, Pakistan Purpose: Many anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy. We explored the relationship of Bax and Bcl-2 gene expression and their ratio with the therapeutic response in acute myeloid leukemia (AML) patients.Patients and methods: Bone marrow and/or blood samples from 90 AML patients treated with cytarabine and daunorubicin were included. Expression of Bax and Bcl-2 was determined through real-time polymerase chain reaction by using ΔΔCt method of relative expression.Results: Bax and Bcl-2 expression among marrow and blood samples correlated with each other (rs=0.5, p