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Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia

INTRODUCTION: The implementation of small-molecule and immunotherapies in acute myeloid leukemia (AML) has been challenging due to genetic and epigenetic variability amongst patients. There are many potential mechanisms by which immune cells could influence small-molecule or immunotherapy responses,...

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Autores principales: Romine, Kyle A., Bottomly, Daniel, Yashar, William, Long, Nicola, Viehdorfer, Matthew, McWeeney, Shannon K., Tyner, Jeffrey W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285384/
https://www.ncbi.nlm.nih.gov/pubmed/37361575
http://dx.doi.org/10.3389/fonc.2023.1192829
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author Romine, Kyle A.
Bottomly, Daniel
Yashar, William
Long, Nicola
Viehdorfer, Matthew
McWeeney, Shannon K.
Tyner, Jeffrey W.
author_facet Romine, Kyle A.
Bottomly, Daniel
Yashar, William
Long, Nicola
Viehdorfer, Matthew
McWeeney, Shannon K.
Tyner, Jeffrey W.
author_sort Romine, Kyle A.
collection PubMed
description INTRODUCTION: The implementation of small-molecule and immunotherapies in acute myeloid leukemia (AML) has been challenging due to genetic and epigenetic variability amongst patients. There are many potential mechanisms by which immune cells could influence small-molecule or immunotherapy responses, yet, this area remains understudied. METHODS: Here we performed cell type enrichment analysis from over 560 AML patient bone marrow and peripheral blood samples from the Beat AML dataset to describe the functional immune landscape of AML. RESULTS: We identify multiple cell types that significantly correlate with AML clinical and genetic features, and we also observe significant correlations of immune cell proportions with ex vivo small-molecule and immunotherapy responses. Additionally, we generated a signature of terminally exhausted T cells (T(ex)) and identified AML with high monocytic proportions as strongly correlating with increased proportions of these immunosuppressive T cells. DISCUSSION: Our work, which is accessible through a new “Cell Type” module in our visualization platform (Vizome; http://vizome.org/), can be leveraged to investigate potential contributions of different immune cells on many facets of the biology of AML.
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spelling pubmed-102853842023-06-23 Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia Romine, Kyle A. Bottomly, Daniel Yashar, William Long, Nicola Viehdorfer, Matthew McWeeney, Shannon K. Tyner, Jeffrey W. Front Oncol Oncology INTRODUCTION: The implementation of small-molecule and immunotherapies in acute myeloid leukemia (AML) has been challenging due to genetic and epigenetic variability amongst patients. There are many potential mechanisms by which immune cells could influence small-molecule or immunotherapy responses, yet, this area remains understudied. METHODS: Here we performed cell type enrichment analysis from over 560 AML patient bone marrow and peripheral blood samples from the Beat AML dataset to describe the functional immune landscape of AML. RESULTS: We identify multiple cell types that significantly correlate with AML clinical and genetic features, and we also observe significant correlations of immune cell proportions with ex vivo small-molecule and immunotherapy responses. Additionally, we generated a signature of terminally exhausted T cells (T(ex)) and identified AML with high monocytic proportions as strongly correlating with increased proportions of these immunosuppressive T cells. DISCUSSION: Our work, which is accessible through a new “Cell Type” module in our visualization platform (Vizome; http://vizome.org/), can be leveraged to investigate potential contributions of different immune cells on many facets of the biology of AML. Frontiers Media S.A. 2023-06-08 /pmc/articles/PMC10285384/ /pubmed/37361575 http://dx.doi.org/10.3389/fonc.2023.1192829 Text en Copyright © 2023 Romine, Bottomly, Yashar, Long, Viehdorfer, McWeeney and Tyner 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
Romine, Kyle A.
Bottomly, Daniel
Yashar, William
Long, Nicola
Viehdorfer, Matthew
McWeeney, Shannon K.
Tyner, Jeffrey W.
Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
title Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
title_full Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
title_fullStr Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
title_full_unstemmed Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
title_short Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
title_sort immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285384/
https://www.ncbi.nlm.nih.gov/pubmed/37361575
http://dx.doi.org/10.3389/fonc.2023.1192829
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