PS1341 CLINICAL SIGNIFICANCE OF KIR GENOTYPE IN JAPANESE PATIENTS WITH MYELODYSPLASTIC SYNDROME

Background: Natural killer (NK) cells have important functions in eradicating tumor and virus‐infected cells without attacking normal cells. Multiple surface receptors are involved in NK cell activities’ regulation, of which the killer immunoglobulin‐like receptor (KIR) plays an important role. There are multiple KIR genes (inhibitory or activated) on chromosome 19q; their number and composition vary with individual and racial differences. The number and/or composition variations of the KIR genes affect the NK cell functions and are associated with the risk of development of certain types of cancers. The patterns of number and combination of the KIR genes are mainly classified as haplotype “A” containing multiple inhibitory KIR genes with a KIR 2DS4 (an activated KIR [ aKIR ]) and haplotype “B” containing various combinations of aKIR and inhibitory KIR genes. In hematological disorders, there are fewer reports on KIR genotype. Here, we focused on Japanese patients with myelodysplastic syndromes (MDS) having normal karyotype to elucidate the clinical significance of KIR genotype in MDS. Aims: To clarify the association of KIR genotype and prognosis in Japanese patients with MDS having normal karyotype. Methods: Genomic DNA was extracted from mononuclear cells that were separated from the bone marrow or peripheral blood samples of patients with MDS. KIR genotype was analyzed in 41 normal karyotype patients with MDS using the KIR genotyping sequence‐specific primers kit. The variations of aKIR content and haplotype and their relationship with MDS progression to acute myeloid leukemia (AML) and survival were investigated. Reported data in Japanese healthy donors were used as control values. Overall survival (OS) and progression‐free survival probabilities were calculated using the Kaplan–Meier method. Results: We compared the prevalence of each KIR between patients with MDS and controls. The inhibitory KIR 3DL1's prevalence was significantly lower in patients with MDS (43.9%) than in controls (99.2%) (Fisher's exact test, P < 0.0001). No significant difference was noted in the total content of aKIR genes between patients with MDS and controls. Further, we investigated the association between the number and/or composition of the KIR genes and the clinical characteristics and outcomes in patients with MDS. The ratio of haplotype A to haplotype B was 1.16:1. Low (0 or 1) and high (≥2) aKIR contents were reported in 17 (41.5%) and 24 patients (58.5%), respectively. We investigated the impact of variations of the KIR genes on the survival and leukemic transformation using Cox proportional hazards model. In univariate analysis, the presence of low aKIR content was associated with the lower risk of progression to AML (HR, 2.59; 95%CI, 0.94–8.25; P = 0.06) and superior OS (HR, 2.35; 95%CI, 0.83–7.60; P = 0.10) compared with high aKIR content. Summary/Conclusion: KIR genotypes’ significance as a prognostic factor for MDS is controversial. A previous study showed low aKIR content an independent risk factor for the progression of MDS to AML. There are various prognostic factors for MDS, including chromosomal abnormalities, and it is difficult to evaluate it with a single factor. In this study, we only analyzed normal karyotype MDS, and low aKIR tended to be a good prognostic factor. Furthermore, the difference in the prevalence of haplotype A population between Japan (54%) and US (26%) may affect our results. Considering the potential NK functions with KIR genotype would improve the understanding of the prognosis and treatment strategy for MDS.