KIR gene haplotype: An independent predictor of clinical outcome in MDS patients

Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and clonal evolution to acute myeloid leukemia (AML). We hypothesized that natural killer (NK) cells and their activating killer immunoglobulin-like receptors (aKIRs) influence the immune surveillance and clinical outcome of patients with MDS. Here, we first examined the distribution of aKIR genes and haplotype in two independent cohorts of MDS and AML patients. The median number of aKIR genes was lower in MDS patients than healthy controls (2 vs. 3 genes, p=0.001), and lower in patients with secondary AML (progressed from MDS) compared to de novo AML patients (2 vs. 3, p=0.008) and healthy controls (2 vs. 3, p=0.006). In a multivariate analysis, the presence of KIR haplotype A (characterized by low aKIR content 0-1) independently predicted a higher risk of conversion to AML (RR with 95% CI, 2.67 [1.13-6.71], p=0.02) and worse adjusted progression-free survival (RR with 95CI, 2.96 [1.59-5.52], p=0.001) and overall survival (2.25 [1.17-4.31], p=0.02), compared to KIR haplotype B (multiple aKIR genes). These novel findings may help to identify MDS patients with a high risk of disease progression, who would likely benefit from adoptive NK cell therapy.