Mechanisms Of Azacitidine Chemotherapy Resistance In Aml And Mds And New Therapy Options

BACKGROUND: TET2 (Ten-eleven-translocation-2) mutations found in 10-30% of MDS and AML patients are actionable for Azacitidine (AZA) treatment (PMID: 21828143). Although response rate of AZA in older AML patients is ~47%, rate of relapse is high due to evolution of disease clones and development of new mutations during treatment cycle. Currently, there is no standard of care for AZA-resistant MDS and AML, and treating these individuals is challenging. Thus, there is an urgent need to identify mechanisms for resistance to AZA for TET2-mutant cancers.