Correlation of the transcription factors IRF4 and BACH2 with the abnormal NFATC1 expression in T cells from chronic myeloid leukemia patients

Hematology. 2022 Dec;27(1):523-529. doi: 10.1080/16078454.2022.2066245.


Objective: T cell dysfunction is a common characteristic of patients with myeloid leukemia and is closely related to clinical efficacy and prognosis. In order to clarify the mechanisms leading to the T cell dysfunction, we characterized the gene expression profile of T cells from chronic myelogenous leukemia (CML) patients by microarray analysis and investigated the related regulating pathway.

Methods: We employed gene expression profiling, bioinformatics and real-time quantitative reverse transcription PCR (RT-qPCR) to detect genes differentially expressed in CML patients versus healthy donors.

Results: There were 1704 genes differentially expressed between CD3+ T cells from CML patients and healthy donors, including 868 up-regulated genes and 836 down-regulated genes, which mostly related to T cell functional pathways. In particular, lower expression of NFATC1, a member of the TCR signaling pathway, was detected in CD3+ T cells from CML patients. We further found that the expression of IRF4 and BACH2, transcription factors that potentially regulate NFATC1, in CD3+ T cells from CML patients was significantly lower than that in healthy donors.

Conclusion: We for the first time observed the altered gene expression profiles of CD3+ T cells from CML patients, and the results suggested that IRF4, BACH2 and NFATC1 may be involved in regulating T cell dysfunction in CML patients in the form of a transcriptional regulatory network. These findings may provide potential targets for tyrosine kinase inhibitors in combination with other targeted immunotherapies .

Keywords: BACH2; CML; IRF4; NFATC1; T cell; T cell dysfunction; immunotherapy.

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Chronic Disease
  • Humans
  • Interferon Regulatory Factors / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myeloid*
  • Lymphocyte Count
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • T-Lymphocytes / metabolism


  • BACH2 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Interferon Regulatory Factors
  • NFATC Transcription Factors
  • NFATC1 protein, human
  • interferon regulatory factor-4