title: KIR gene haplotype: an independent predictor of clinical outcome in MDS patients.
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.
authors.affiliation: Department of Haematology, Hammersmith Hospital, Imperial College London, London, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Stringaris
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.affiliation: Centre for Trials Research, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Hills
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sobieski
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Kai
authors.initials: K
authors.lastname: Cao
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Jerome G
authors.initials: JG
authors.lastname: Saltarrelli
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: May
authors.initials: M
authors.lastname: Daher
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Hila
authors.initials: H
authors.lastname: Shaim
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Smith
authors.affiliation: Department of Haematology, UCL Cancer Institute, University College London, London, United Kingdom; and.
authors.forename: David
authors.initials: D
authors.lastname: Linch
authors.affiliation: Department of Haematology, UCL Cancer Institute, University College London, London, United Kingdom; and.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Gale
authors.affiliation: Department of Haematology, UCL Cancer Institute, University College London, London, United Kingdom; and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Allen
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sekine
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Rohtesh
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Leukemia Department, MD Anderson Cancer Center, Houston, TX.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Leukemia Department, MD Anderson Cancer Center, Houston, TX.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D054340:Receptors, KIR / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054340:Receptors, KIR