PURPOSE: Killer-cell immunoglobulin-like receptors (KIRs) that regulate natural-killer cells are highly polymorphic. Some KIR2DL1 alleles encode receptors that have stronger signaling function than others. We tested the hypothesis that the clinical outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT) could be affected by donor KIR2DL1 polymorphism. PATIENTS AND METHODS: All 313 pediatric patients received allogeneic HSCT at a single institution. Donor KIR2DL1 functional allele typing was retrospectively performed using single nucleotide polymorphism assay. RESULTS: Patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R(245)) had better survival (P = .0004) and lower cumulative incidence of disease progression (P = .001) than those patients who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C(245)). The effect of KIR2DL1 allelic polymorphism was similar in patients with acute myeloid leukemia or acute lymphoblastic leukemia among all allele groups (P ≥ .71). Patients who received a KIR2DL1-R(245)-positive graft with HLA-C receptor-ligand mismatch had the best survival (P = .00003) and lowest risk of leukemia progression (P = .0005) compared with those who received a KIR2DL1-C(245) homozygous graft. CONCLUSION: Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.
PURPOSE: Killer-cell immunoglobulin-like receptors (KIRs) that regulate natural-killer cells are highly polymorphic. Some KIR2DL1 alleles encode receptors that have stronger signaling function than others. We tested the hypothesis that the clinical outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT) could be affected by donorKIR2DL1 polymorphism. PATIENTS AND METHODS: All 313 pediatric patients received allogeneic HSCT at a single institution. DonorKIR2DL1 functional allele typing was retrospectively performed using single nucleotide polymorphism assay. RESULTS:Patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R(245)) had better survival (P = .0004) and lower cumulative incidence of disease progression (P = .001) than those patients who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C(245)). The effect of KIR2DL1 allelic polymorphism was similar in patients with acute myeloid leukemia or acute lymphoblastic leukemia among all allele groups (P ≥ .71). Patients who received a KIR2DL1-R(245)-positive graft with HLA-C receptor-ligand mismatch had the best survival (P = .00003) and lowest risk of leukemia progression (P = .0005) compared with those who received a KIR2DL1-C(245) homozygous graft. CONCLUSION:DonorKIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.
Authors: Sarah Cooley; Daniel J Weisdorf; Lisbeth A Guethlein; John P Klein; Tao Wang; Chap T Le; Steven G E Marsh; Daniel Geraghty; Stephen Spellman; Michael D Haagenson; Martha Ladner; Elizabeth Trachtenberg; Peter Parham; Jeffrey S Miller Journal: Blood Date: 2010-06-25 Impact factor: 22.113
Authors: Janelle A Olson; Dennis B Leveson-Gower; Saar Gill; Jeanette Baker; Andreas Beilhack; Robert S Negrin Journal: Blood Date: 2010-03-16 Impact factor: 22.113
Authors: Chul-Woo Pyo; Lisbeth A Guethlein; Quyen Vu; Ruihan Wang; Laurent Abi-Rached; Paul J Norman; Steven G E Marsh; Jeffrey S Miller; Peter Parham; Daniel E Geraghty Journal: PLoS One Date: 2010-12-29 Impact factor: 3.240
Authors: Nirali N Shah; Kristin Baird; Cynthia P Delbrook; Thomas A Fleisher; Mark E Kohler; Shakuntala Rampertaap; Kimberly Lemberg; Carolyn K Hurley; David E Kleiner; Melinda S Merchant; Stefania Pittaluga; Marianna Sabatino; David F Stroncek; Alan S Wayne; Hua Zhang; Terry J Fry; Crystal L Mackall Journal: Blood Date: 2014-12-01 Impact factor: 22.113
Authors: S Nguyen; A Achour; L Souchet; S Vigouroux; P Chevallier; S Furst; A Sirvent; J-O Bay; G Socié; P Ceballos; A Huynh; J Cornillon; S Francois; F Legrand; I Yakoub-Agha; G Michel; N Maillard; G Margueritte; S Maury; M Uzunov; C-E Bulabois; M Michallet; L Clement; C Dauriac; K Bilger; J Lejeune; V Béziat; V Rocha; B Rio; S Chevret; V Vieillard Journal: Bone Marrow Transplant Date: 2017-06-26 Impact factor: 5.483
Authors: Seth E Karol; Elaine Coustan-Smith; Xueyuan Cao; Sheila A Shurtleff; Susana C Raimondi; John K Choi; Raul C Ribeiro; Gary V Dahl; William Paul Bowman; Jeffrey W Taub; Barbara Degar; Wing Leung; James R Downing; Ching-Hon Pui; Jeffrey E Rubnitz; Dario Campana; Hiroto Inaba Journal: Br J Haematol Date: 2014-08-28 Impact factor: 6.998