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Updated: Jul 8, 2025

Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution
Published on: February 24, 2015
Mechanisms of resistance to hypomethylating agents and BCL-2 inhibitors
Sudhamsh Reddy Desai1, Samarpana Chakraborty2, Aditi Shastri3
1Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Abstract:
Myeloid malignancies such as myelodysplastic syndrome (MDS) & acute myeloid leukemia (AML) are clonal diseases that emerge and progress due to the expansion of disease-initiating aberrant hematopoietic stem cells, that are not eliminated by conventional cytotoxic therapies. Hypomethylating agents(HMA), azacytidine and decitabine are the first line agents for treatment of MDS and a combination with BCL-2 inhibitor, venetoclax, is approved for AML induction in patients above 75 years and is also actively being investigated for use in high risk MDS. Resistance to these drugs has become a significant clinical challenge in treatment of myeloid malignancies. In this review, we discuss molecular mechanisms underlying the development of resistance to HMA and venetoclax. Insights into these mechanisms can help identify potential biomarkers for resistance prediction, aid in the development of combination therapies and strategies to prevent resistance and advance the field of cancer therapeutics.
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