Work

Beyond initial response: Acquired resistance to hypomethylating agents in myeloid malignancies

Year: 2026

Type: article

Abstract: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are haematological malignancies characterized by the uncontrolled proliferation of immature, dysplastic myeloid stem and progenitor cells. These diseases exist on a biological continuum, with many MDS patients eventually progressing to AML. Both conditions predominantly affect older adults, who are often ineligible for intensive chemotherapy and stem cell transplantation due to comorbidities and frailty. For such patients, hypomethylating agents (HMAs) represent a critical therapeutic option, offering lower-intensity treatment that can induce temporary remission and extend survival. However, HMA responses are transient, with inevitable resistance leading to fatal relapse. Despite the clinical significance of HMA resistance, the underlying mechanisms remain poorly understood, and effective treatment strategies for HMA-relapsed disease are lacking. This review provides a comprehensive update on the current clinical use of HMA-based therapies in AML and MDS, and highlights the significant challenge of relapse. We then summarise available data on the molecular features of acquired HMA resistance, revealing complex and inter-connected drivers of disease recurrence.

Source: Critical Reviews in Oncology/Hematology

DOI: 10.1016/j.critrevonc.2026.105228

Authors: Brooke M. Harvey, Anoop K. Enjeti, Danielle R. Bond, Heather J. Lee

Institutions: Hunter Medical Research Institute, University of Newcastle Australia, Calvary Mater Newcastle Hospital

Language: English

Topic: Acute Myeloid Leukemia Research

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,190