Molecular insights and treatment innovations: Advancing outcomes in acute myeloid leukemia with myelodysplasia‑related changes (Review).

Abstract

Acute myeloid leukemia, myelodysplasia‑related (AML‑MR), a challenging and aggressive subtype of AML, is characterized by unique genetic abnormalities and molecular features, which contribute to its poor prognosis compared with other AML subtypes. The present review summarizes the current understanding of AML‑MR pathogenesis, highlighting notable advancements in genetic and cytogenetic insights. Critical mutations, such as those in the tumor antigen p53 and additional sex combs like 1 genes, and their role in disease progression and resistance to treatment, are explored. The review further investigates how clonal evolution and cellular microenvironment alterations drive AML‑MR transformation and impact patient outcomes. Despite the poor outlook typically associated with AML‑MR, developments in treatment approaches offer hope. The present review considers the efficacy of novel therapeutic agents, including CPX‑351, hypomethylating agents and targeted molecular therapies. Additionally, innovations in immunotherapy and allogeneic hematopoietic stem cell transplantation are discussed as promising avenues to improve patient survival rates. The challenges of treating AML‑MR, particularly in elderly and pretreated patients, underline the necessity for individualized treatment strategies that consider both the biological complexity of the disease and the overall health profile of the patient. The present review focuses on the mechanisms of AML‑MR transformation, highlighting factors that may offer a crucial theoretical foundation and pave the way for future applications in precision medicine. Future research directions include exploring novel targeted therapies and combination regimens to mitigate the transformation risks and enhance the quality of life of patients with AML‑MR.