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The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate

FLT3 mutations are very frequent in AML and utilization of FLT3 inhibitors as approved treatment options are very common. Despite the initial success of inhibitor treatment, the development of resistances against this treatment is a major challenge in AML therapy. One of the mechanisms causing resis...

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Autores principales: Klement, Laura, Drube, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577206/
https://www.ncbi.nlm.nih.gov/pubmed/37849810
http://dx.doi.org/10.3389/fonc.2023.1258679
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author Klement, Laura
Drube, Julia
author_facet Klement, Laura
Drube, Julia
author_sort Klement, Laura
collection PubMed
description FLT3 mutations are very frequent in AML and utilization of FLT3 inhibitors as approved treatment options are very common. Despite the initial success of inhibitor treatment, the development of resistances against this treatment is a major challenge in AML therapy. One of the mechanisms causing resistance is the homing of the leukemic cells in the protective niche of the bone marrow microenvironment (BMM). A pathway mediating homing to the BMM and leukemic cell survival is the CXCL12/CXCR4 axis. The analysis of patient samples in several independent studies indicated that FLT3-ITD expression led to higher CXCR4 surface expression. However, several in vitro studies reported contradictory findings, suggesting that FLT3-ITD signaling negatively influenced CXCR4 expression. In this commentary, we provide an overview summarizing the studies dealing with the relationship of FLT3 and CXCR4. Taken together, the current research status is not sufficient to answer the question whether FLT3 and CXCR4 act together or independently in leukemia progression. Systematic analyses in model cell systems are needed to understand the interplay between FLT3 and CXCR4, since this knowledge could lead to the development of more effective treatment strategies for AML patients.
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spelling pubmed-105772062023-10-17 The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate Klement, Laura Drube, Julia Front Oncol Oncology FLT3 mutations are very frequent in AML and utilization of FLT3 inhibitors as approved treatment options are very common. Despite the initial success of inhibitor treatment, the development of resistances against this treatment is a major challenge in AML therapy. One of the mechanisms causing resistance is the homing of the leukemic cells in the protective niche of the bone marrow microenvironment (BMM). A pathway mediating homing to the BMM and leukemic cell survival is the CXCL12/CXCR4 axis. The analysis of patient samples in several independent studies indicated that FLT3-ITD expression led to higher CXCR4 surface expression. However, several in vitro studies reported contradictory findings, suggesting that FLT3-ITD signaling negatively influenced CXCR4 expression. In this commentary, we provide an overview summarizing the studies dealing with the relationship of FLT3 and CXCR4. Taken together, the current research status is not sufficient to answer the question whether FLT3 and CXCR4 act together or independently in leukemia progression. Systematic analyses in model cell systems are needed to understand the interplay between FLT3 and CXCR4, since this knowledge could lead to the development of more effective treatment strategies for AML patients. Frontiers Media S.A. 2023-10-02 /pmc/articles/PMC10577206/ /pubmed/37849810 http://dx.doi.org/10.3389/fonc.2023.1258679 Text en Copyright © 2023 Klement and Drube https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Klement, Laura
Drube, Julia
The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate
title The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate
title_full The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate
title_fullStr The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate
title_full_unstemmed The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate
title_short The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate
title_sort interplay of flt3 and cxcr4 in acute myeloid leukemia: an ongoing debate
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577206/
https://www.ncbi.nlm.nih.gov/pubmed/37849810
http://dx.doi.org/10.3389/fonc.2023.1258679
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