Faculty, Staff and Student Publications

Publication Date

6-1-2025

Journal

Current Opinion in Pharmacology

DOI

10.1016/j.coph.2025.102526

PMID

40318269

PMCID

PMC12084123

PubMedCentral® Posted Date

6-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs' functional heterogeneity, complicates targeted treatment approaches. Immune dysfunction, including T cell exhaustion and immune suppression within the bone marrow niche contributes to therapy resistance. In this brief review, we aim to explore current challenges in AML therapy, focusing on LSC-driven resistance, immune evasion, and the need for innovative therapeutic strategies.

Keywords

Humans, Leukemia, Myeloid, Acute, Neoplastic Stem Cells, Animals, Inflammation, Antineoplastic Agents, Drug Resistance, Neoplasm

Published Open-Access

yes

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