Language

English

Publication Date

11-1-2024

Journal

Experimental & Molecular Medicine

DOI

10.1038/s12276-024-01335-7

PMID

39482533

PMCID

PMC11612169

PubMedCentral® Posted Date

11-1-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Current intensified chemotherapy regimens have significantly increased survival rates for pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL), but these treatments can result in serious adverse effects; furthermore, patients who are resistant to chemotherapy or who relapse have inferior outcomes, together highlighting the need for improved therapeutic strategies. Despite recent advances in stratifying T-ALL into molecular subtypes with distinct driver mutations, efforts to target the tumor-intrinsic genomic alterations critical for T-ALL progression have yet to translate into more effective and less toxic therapies. Ample evidence now indicates that extrinsic factors in the leukemic microenvironment are critical for T-ALL growth, infiltration, and therapeutic resistance. Considering the diversity of organs infiltrated by T-ALL cells and the unique cellular components of the microenvironment encountered at each site, it is likely that there are both shared features of tumor-supportive niches across multiple organs and site-specific features that are key to leukemia cell survival. Therefore, elucidating the distinct microenvironmental cues supporting T-ALL in different anatomic locations could reveal novel therapeutic targets to improve therapies. This review summarizes the current understanding of the intricate interplay between leukemia cells and the diverse cells they encounter within their tumor microenvironments (TMEs), as well as opportunities to therapeutically target the leukemic microenvironment.

Keywords

Animals, Humans, Disease Progression, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Signal Transduction, Tumor Microenvironment, Cancer microenvironment, Acute lymphocytic leukaemia

Published Open-Access

yes

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