Is KIR gene useful in predicting the clinical outcome of MDS?

Natural Killer (NK) cells partly mediate immune responses against Myelodysplastic Syndrome (MDS) and this can potentially affect disease progression. NK cells express both activating and inhibitory Killer Immunoglobulin-like Receptors (KIRs) that interact and mediate NK effector function. Based on the number of inherited KIR genes, individuals can be divided into two haplotype groups: haplotype A (comprises of five inhibitory KIR genes and a single Activating KIR [aKIR] gene) and haplotype B (comprises various combinations of aKIR genes and inhibitory KIR genes). 

Dr Kate Stringaris from Hammersmith Hospital, Imperial College, London, and colleagues recently published the findings of their study, which is on the variations of aKIR gene content and haplotype in MDS and their association to progression to Acute Myeloid Leukemia (AML) and survival. The data obtained were first published ahead of print on 19 October 2016 in Blood.  

Highlights:

• 108 MDS patients were included in this study  
• Median number of aKIR genes in MDS patients vs control: 2 vs 3, P = 0.001
• Median number of aKIR genes in secondary AML patients vs de novo AML patients: 2 vs 3, P = 0.008
• 4-year probability of progression to AML patients with KIR haplotype A & KIR haplotype B: 37.1 vs 16.8, P = 0.02
• 4-year Progression Free Survival (PFS) of patients with KIR haplotype A & KIR haplotype B: 27.3 vs 48.9, P = 0.02
• 4-year Overall Survival (OS) of patients with KIR haplotype A & KIR haplotype B: 31.2 vs 48.2, P = 0.02
• Compared to haplotype B, haplotype A had a worse adjusted PFS and OS; (Relative Risk [RR] with 95% CI: 2.96 [1.59–5.52], P = 0.001) and (2.25 [1.17–4.31], P = 0.02)
• RR of conversion to AML in patients with haplotype A vs haplotype B: 2.67 (1.13–6.31), P = 0.02

The authors concluded by stating that their findings show an association between aKIR gene content and MDS-AML transformation. This association could be used to identify a subgroup of MDS patients with a high risk of disease progression and poor outcome who would benefit from adoptive NK cell therapy. A poster based on their findings was presented at a session held on the 5 December 2016 at the American Society of Hematology Meeting in San Diego.  

Abstract

Myelodysplastic syndromes (MDSs) 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 MDSs. Here, we first examined the distribution of aKIR genes and haplotype in 2 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 = .001), and lower in patients with secondary AML (progressed from MDSs) compared with de novo AML patients (2 vs 3; P = .008) and healthy controls (2 vs 3; P = .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 (relative risk [RR] with 95% confidence interval [CI], 2.67 [1.13-6.71]; P = .02) and worse adjusted progression-free survival (RR with 95% CI, 2.96 [1.59-5.52]; P = .001) and overall survival (2.25 [1.17-4.31]; P = .02), compared with 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.