Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)

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 h...

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Main Authors: Aram Lyu, Seo Hee Nam, Ryan S. Humphrey, Terzah M. Horton, Lauren I. R. Ehrlich
Format: Article
Language:English
Published: Nature Publishing Group 2024-11-01
Series:Experimental and Molecular Medicine
Online Access:https://doi.org/10.1038/s12276-024-01335-7
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author Aram Lyu
Seo Hee Nam
Ryan S. Humphrey
Terzah M. Horton
Lauren I. R. Ehrlich
author_facet Aram Lyu
Seo Hee Nam
Ryan S. Humphrey
Terzah M. Horton
Lauren I. R. Ehrlich
author_sort Aram Lyu
collection DOAJ
description 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.
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spelling doaj-art-c9601a89682745138a1ec20665d2b82f2024-12-08T12:19:43ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132024-11-0156112337234710.1038/s12276-024-01335-7Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)Aram Lyu0Seo Hee Nam1Ryan S. Humphrey2Terzah M. Horton3Lauren I. R. Ehrlich4Division of Hematology/Oncology, Department of Medicine, University of CaliforniaDepartment of Molecular Biosciences, The University of Texas at AustinDepartment of Molecular Biosciences, The University of Texas at AustinDepartment of Pediatrics, Baylor College of Medicine/Dan L. Duncan Cancer Center and Texas Children’s Cancer CenterDepartment of Molecular Biosciences, The University of Texas at AustinAbstract 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.https://doi.org/10.1038/s12276-024-01335-7
spellingShingle Aram Lyu
Seo Hee Nam
Ryan S. Humphrey
Terzah M. Horton
Lauren I. R. Ehrlich
Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)
Experimental and Molecular Medicine
title Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)
title_full Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)
title_fullStr Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)
title_full_unstemmed Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)
title_short Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)
title_sort cells and signals of the leukemic microenvironment that support progression of t cell acute lymphoblastic leukemia t all
url https://doi.org/10.1038/s12276-024-01335-7
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