FLT3LG and IFITM3P6 consolidate T cell activity in the bone marrow microenvironment and are prognostic factors in acute myelocytic leukemia

Haiyan Chen; Haiyan Chen; Meng Wu; Hongping Xia; Songjie Du; Guoren Zhou; Guangfeng Long; Yanan Zhu; Xu Huang; Daheng Yang

doi:10.3389/fimmu.2022.980911

Frontiers in Immunology (Aug 2022)

FLT3LG and IFITM3P6 consolidate T cell activity in the bone marrow microenvironment and are prognostic factors in acute myelocytic leukemia

Haiyan Chen,
Haiyan Chen,
Meng Wu,
Hongping Xia,
Songjie Du,
Guoren Zhou,
Guangfeng Long,
Yanan Zhu,
Xu Huang,
Daheng Yang

Affiliations

Haiyan Chen: Institute for Cancer Research, School of Basic Medical Science of Xi’an Jiaotong University, Xi’an, China
Haiyan Chen: Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China
Meng Wu: Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China
Hongping Xia: Department of Pathology, School of Basic Medical Sciences & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, China
Songjie Du: Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Guoren Zhou: Jiangsu Cancer Hospital & The Affifiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China
Guangfeng Long: Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China
Yanan Zhu: Translational Medicine Institute, Xi’an Jiaotong University Health Science Center, Xi’an, China
Xu Huang: Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China
Daheng Yang: Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China

DOI: https://doi.org/10.3389/fimmu.2022.980911
Journal volume & issue: Vol. 13

Abstract

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Acute myelocytic leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage. CD4+ and CD8+ T cells play pivotal roles in influencing AML progression but are functionally suppressed in the bone marrow microenvironment. We aimed to find hub genes related to T cell exhaustion and suppression, thereby providing evidence for immunotherapy. In this study, gene transcriptome expression data from TCGA and TARGET databases were utilized to find key genes. Firstly, CIBERSORT immune cell infiltration algorithm and WGCNA method were used to identify CD4+ and CD8+ T cells-related genes. Univariate and multivariate cox regression analyses were then introduced to construct the overall survival prognosis model and included hub genes. The ESTIMATE and ssGSEA scoring methods were used to analyze the correlation between the hub genes and immune activity. Single-cell transcriptome analysis was applied to detect the immune cells expressing hub genes, hence, to detect exact mechanisms. Consequently, FLT3LG and IFITM3P6 were determined to be positively correlated with patients’ overall survival and microenvironment immune activity. Further study suggested FLT3-FLT3LG and IFITM3P6-miR-6748-3p-CBX7 signaling axes were involved in CD4+ and CD8+ T cells activation. This may be one of the mechanisms of T cells suppression in AML.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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