Increasedinterferon regulatory factor 4 (IRF4) gene expression is associated with an increased susceptibility to de novo acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), according to research in Frontiers in Genetics.

The authors of the genome-wide association study (GWAS) sought to determine genetic variations and their role in susceptibility to AML and MDS.

They used data from the DISCOVeRY-BMT (Determining the Influence of Susceptibility COnveying Variants Related to one-Year mortality after BMT) study, which included 1769 patients with AML, 540 patients with MDS, and 2814 control donors.

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The authors used ASSET tests to address disease heterogeneity, and used transcriptome-wide association study (TWAS) to test the association of gene expression with disease risk.

IRF4 is a transcription factor that regulates myeloid and lymphoid hematopoietic differentiation. Patients carrying a T allele at rs12203592 in IRF4 who had undergone unrelated donor bone marrow transplant (URD-BMT) had an increased risk for the development of de novo AML and MDS and therapy related MDS (t-MDS) (odds ratio [OR], 1.38). Therapy-related AML (t-AML) was not associated with rs12203592.

The study authors also found an association between higher expression of AKT1 and de novo AML and MDS.

Overexpression of IRF4 has previously been identified in GWAS of diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary effusion lymphoma, as found in previous studies. The current research adds to the understanding of the risk loci of AML and MDS.

Despite the large study population, the patients were mostly non-Hispanic European Americans. Future studies should evaluate the findings in a cohort of nonwhite patients.


Wang J, Clay-Gilmour AI, Karaesmen E, et al. Genome-wide association analyses identify variants in IRF4 associated with acute myeloid leukemia and myelodysplastic syndrome susceptibility. Front Genet. 2021;12:554948. doi:10.3389/fgene.2021.554948