Journal article
Acute myeloid leukemia resistant to venetoclax-based therapy: What does the future hold?
Blood reviews, Vol.59, 101036
05/2023
DOI: 10.1016/j.blre.2022.101036
PMID: 36549969
Abstract
Venetoclax is a highly selective B-cell lymphoma-2 (BCL-2) inhibitor, which, combined with a DNA hypomethylating agent or low dose cytarabine, results in high rates of initial responses in patients with acute myeloid leukemia (AML). However, the disease relapses in most patients. Mechanisms of resistance to venetoclax-based therapy include TP53 gene mutations or inactivation of p53 protein, activating kinase mutations such as FLT3 and RAS, and upregulation of other BCL-2 family apoptotic proteins. Current clinical trials are exploring strategies such as doublet or triplet regimens incorporating a p53 activator, an anti-CD47 antibody, or other novel agents that target genes and proteins responsible for resistance to venetoclax. Further studies should focus on identifying predictive biomarkers of response to venetoclax-based therapy and incorporating immunotherapeutic approaches such as checkpoint inhibitors, bispecific antibodies, antibody-drug conjugates, and CAR T-cell therapy to improve outcomes for patients with AML.
Details
- Title: Subtitle
- Acute myeloid leukemia resistant to venetoclax-based therapy: What does the future hold?
- Creators
- Prajwal Dhakal - Department of Internal Medicine, Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, 200 Hawkins Dr. C 21GH, Iowa City, IA 52245, United States of America. Electronic address: prajwal-dhakal@uiowa.eduMelissa Bates - Department of Internal Medicine, Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, 200 Hawkins Dr. C 21GH, Iowa City, IA 52245, United States of America. Electronic address: melissa-bates@uiowa.eduMichael H Tomasson - Department of Internal Medicine, Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, 200 Hawkins Dr. C 21GH, Iowa City, IA 52245, United States of America. Electronic address: michael-tomasson@uiowa.eduGrerk Sutamtewagul - Department of Internal Medicine, Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, 200 Hawkins Dr. C 21GH, Iowa City, IA 52245, United States of America. Electronic address: grerk-sutamtewagul@uiowa.eduAdam Dupuy - Department of Anatomy & Cell Biology, University of Iowa, 375 Newton Road, 3202 MERF, Iowa City, IA 52242, United States of America. Electronic address: adam-dupuy@uiowa.eduVijaya Raj Bhatt
- Resource Type
- Journal article
- Publication Details
- Blood reviews, Vol.59, 101036
- DOI
- 10.1016/j.blre.2022.101036
- PMID
- 36549969
- ISSN
- 0268-960X
- eISSN
- 1532-1681
- Language
- English
- Electronic publication date
- 12/01/2022
- Date published
- 05/2023
- Academic Unit
- Anatomy and Cell Biology; Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Pathology; Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984339407102771
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