TY - JOUR
T1 - KIR gene haplotype
T2 - An independent predictor of clinical outcome in MDS patients
AU - Stringaris, Kate
AU - Marin, David
AU - Barrett, A. John
AU - Hills, Robert
AU - Sobieski, Catherine
AU - Cao, Kai
AU - Saltarrelli, Jerome G.
AU - Daher, May
AU - Shaim, Hila
AU - Smith, Nathaniel
AU - Linch, David
AU - Gale, Rosemary
AU - Allen, Christopher
AU - Sekine, Takuya
AU - Mehta, Rohtesh
AU - Champlin, Richard
AU - Shpall, Elizabeth J.
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
AU - Rezvani, Katayoun
N1 - Publisher Copyright:
© 2016, American Society of Hematology. All rights reserved.
PY - 2016/12/15
Y1 - 2016/12/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2016-05-713099
DO - 10.1182/blood-2016-05-713099
M3 - Article
C2 - 27760759
AN - SCOPUS:85014948898
SN - 0006-4971
VL - 128
SP - 2819
EP - 2823
JO - Blood
JF - Blood
IS - 24
ER -