Presence of LILRB4 SNP rs1048801 modulates acute myeloid leukemia progression and inhibits CD4+ T cells proliferation.

Abstract

Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4), an emerging immune checkpoint molecule, exhibits therapeutic potential in acute myeloid leukemia (AML). While single nucleotide polymorphisms (SNPs) of immune checkpoint genes have been extensively investigated in AML, the association between LILRB4 genetic polymorphisms and clinical outcomes remains unexplored. We investigated SNPs within the LILRB4 immunoglobulin domain and immunoreceptor tyrosine-based inhibitory motif regions in 151 AML patients and 203 controls. The rs1048801 G allele was significantly associated with increased LILRB4 mRNA expression, higher disease susceptibility, and reduced overall survival. Functional studies revealed that the G allele enhanced AML cell proliferation and colony formation. Furthermore, protein-protein interaction network analysis identified CD4 as a pivotal downstream mediator of LILRB4. Flow cytometry revealed elevated LILRB4 expression in CD45+ leukocytes and CD45+ CD33+ CD14+ monocytic AML cells from G allele carriers, concomitant with reduced CD3+ CD4+ T cell populations and impaired proliferation. Collectively, these findings establish rs1048801 as a critical modulator of AML progression through LILRB4-mediated CD4+ T cell suppression, providing new insights for personalized therapeutic strategies.