ISSN 2997-1036
International Journal of Hematology | Vol. 7, No. 1, January 2016 | pp. 1–8
DOI: 10.46882/2016/IJH/000073
Review Article
Title: Structural mechanisms and targeted chemical inhibition of the BCL-2 pathways in acute myeloid leukemia cells
Names of Authors: M. A. Bello¹, O. R. Eze²
Authors’ Affiliations: ¹Department of Haematology, Aminu Kano Teaching Hospital, Kano, Nigeria; ²Department of Pathology, University of Benin, Benin City, Nigeria
Abstract: Evading apoptosis is a foundational hallmark of hematological malignancies, heavily driven by the upregulation of anti-apoptotic B-cell lymphoma 2 (BCL-2) family proteins. This comprehensive review examines the molecular structural mechanisms of BCL-2 mediated survival in acute myeloid leukemia blasts, focusing on the competitive interaction dynamics between pro-apoptotic BH3-only proteins and downstream mitochondrial outer membrane permeabilization cascades. Traditional cytotoxic chemotherapy often fails to clear leukemia stem cells that overexpress BCL-2. Evolving therapeutic paradigms emphasize the selective deployment of small-molecule BH3 mimetics, such as venetoclax, which competitively binds the hydrophobic groove of BCL-2 to displace pro-apoptotic factors. Combining venetoclax with low-dose cytarabine or hypomethylating backbones has demonstrated high complete remission rates in elderly or treatment-naive acute myeloid leukemia populations unsuitable for intensive induction. However, secondary drug resistance mechanisms, such as upregulation of MCL-1 or BAX mutations, present ongoing clinical challenges. This review details practical biomarker-driven strategies and clinical combination pathways designed to bypass intrinsic resistance and maximize clonal eradication in myeloid leukemias.
Keywords: Acute myeloid leukemia, BCL-2 pathway, venetoclax, apoptosis, BH3 mimetics
Manuscript Timeline: Received: October 12, 2015; Revised: November 22, 2015; Accepted: December 10, 2015; Published: January 16, 2016