TY - JOUR
T1 - Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia
AU - Romine, Kyle A.
AU - Bottomly, Daniel
AU - Yashar, William
AU - Long, Nicola
AU - Viehdorfer, Matthew
AU - McWeeney, Shannon K.
AU - Tyner, Jeffrey W.
N1 - Publisher Copyright:
Copyright © 2023 Romine, Bottomly, Yashar, Long, Viehdorfer, McWeeney and Tyner.
PY - 2023
Y1 - 2023
N2 - 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 (Tex) 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.
AB - 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 (Tex) 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.
KW - AML – acute myeloid leukemia
KW - RNAseq analysis
KW - checkpoint inhibition therapy
KW - functional genomic data
KW - immune therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85162695385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85162695385&partnerID=8YFLogxK
U2 - 10.3389/fonc.2023.1192829
DO - 10.3389/fonc.2023.1192829
M3 - Article
AN - SCOPUS:85162695385
SN - 2234-943X
VL - 13
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1192829
ER -