STAT signaling in the pathogenesis and therapy of acute myeloid leukemia and myelodysplastic syndromes

Zoe King; Sudhamsh Reddy Desai; David A Frank; Aditi Shastri

doi:10.1016/j.neo.2025.101137

STAT signaling in the pathogenesis and therapy of acute myeloid leukemia and myelodysplastic syndromes

Neoplasia. 2025 Mar:61:101137. doi: 10.1016/j.neo.2025.101137. Epub 2025 Feb 10.

Authors

Zoe King¹, Sudhamsh Reddy Desai², David A Frank³, Aditi Shastri⁴

Affiliations

¹ Department of Pediatric Hematology and Oncology, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
² Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
³ Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: David.alan.frank@emory.edu.
⁴ Department of Oncology, Montefiore Medical Center & Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: ashastri@montefiore.org.

Abstract

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent complex hematopoietic malignancies characterized by ineffective hematopoiesis and dysregulated myeloid differentiation. Recent research has underscored the critical role of aberrant STAT signaling pathways, particularly involving STAT3 and STAT5, in the pathogenesis of these disorders. Aberrant activation of STAT proteins has been implicated as a mediator of oncogenesis in several malignancies. In this review, we discuss the role of STAT proteins in both regulated and dysregulated hematopoiesis, the consequences of dysregulation in acute myeloid leukemia and myelodysplastic syndromes, therapeutic strategies, and recent advancements in STAT-targeted therapy. By integrating findings from recent preclinical and clinical studies, this review provides insights into the evolving landscape of STAT-targeted therapies, highlighting the promise of these approaches in enhancing treatment efficacy and improving patient outcomes in high-risk hematologic malignancies.

Keywords: Acute myeloid leukemia; Myelodysplastic syndromes; STAT proteins; Therapeutic strategies; Transcription factors.

Publication types

Review

MeSH terms

Animals
Hematopoiesis
Humans
Leukemia, Myeloid, Acute* / drug therapy
Leukemia, Myeloid, Acute* / etiology
Leukemia, Myeloid, Acute* / metabolism
Leukemia, Myeloid, Acute* / pathology
Leukemia, Myeloid, Acute* / therapy
Molecular Targeted Therapy
Myelodysplastic Syndromes* / drug therapy
Myelodysplastic Syndromes* / etiology
Myelodysplastic Syndromes* / metabolism
Myelodysplastic Syndromes* / pathology
Myelodysplastic Syndromes* / therapy
STAT Transcription Factors* / genetics
STAT Transcription Factors* / metabolism
Signal Transduction* / drug effects

Substances

STAT Transcription Factors