Mechanisms of resistance to hypomethylating agents and BCL-2 inhibitors

Sudhamsh Reddy Desai, Samarpana Chakraborty, Aditi Shastri

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Article number101521
JournalBest Practice and Research: Clinical Haematology
Issue number4
StatePublished - Dec 2023


  • AML
  • Azacytidine
  • Decitabine
  • Therapy resistance
  • Venetoclax

ASJC Scopus subject areas

  • Oncology
  • Clinical Biochemistry


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