Association of HLA‐E single nucleotide polymorphisms with human myeloid leukemia

Single nucleotide polymorphisms (SNPs) of HLA‐E are related to the occurrence of many diseases, but their functions remain unclear. In this study, the function of SNPs at HLA‐E rs76971248 and rs1264457 on the myeloid leukemia cells was analyzed by a progressive procedure, included genotyping, mRNA transcription, regulatory element, protein expression, and anti‐tumor effect. The frequencies of rs76971248 G and rs1264457 G were found higher in myeloid leukemia patients than those in healthy blood donors ( p < 0.05). For myeloid leukemia, rs76971248 T was protective, while rs1264457 G was susceptible. We also found that rs76971248 affected HLA‐E mRNA transcription and membrane HLA‐E (mHLA‐E) expression in K562 cells through differently binding to transcription factor HOXA5 ( p < 0.0001), while rs1264457 affected mHLA‐E expression by changing mRNA transcription and an encoding amino acid ( p < 0.01). In contrast, the expression of soluble HLA‐E (sHLA‐E) was not influenced by both rs1264457 and rs76971248. The higher HLA‐E expression was detected among myeloid leukemia patients, and the K562 cells with higher HLA‐E molecules played a significant inhibitory effect on the killing activity of NK‐92MI cells ( p < 0.05). In conclusion, the higher HLA‐E expression of myeloid leukemia cells is promoted by rs76971248 G and rs1264457 G, which helps escape from NK‐92MI cells' killing.