title: Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric allogeneic hematopoietic stem-cell transplantation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.
authors.affiliation: Rafijul Bari, Piya Rujkijyanont, Erin Sullivan, Guolian Kang, Victoria Turner, Kwan Gan, Wing Leung, St Jude Children's Research Hospital; Wing Leung, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Rafijul
authors.initials: R
authors.lastname: Bari
authors.forename: Piya
authors.initials: P
authors.lastname: Rujkijyanont
authors.forename: Erin
authors.initials: E
authors.lastname: Sullivan
authors.forename: Guolian
authors.initials: G
authors.lastname: Kang
authors.forename: Victoria
authors.initials: V
authors.lastname: Turner
authors.forename: Kwan
authors.initials: K
authors.lastname: Gan
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
mesh_terms: D000293:Adolescent; D000483:Alleles; D000704:Analysis of Variance; D001120:Arginine; D002648:Child; D002675:Child, Preschool; D003545:Cysteine; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015236:HLA-C Antigens; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000601:surgery*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000601:surgery*; D054342:Receptors, KIR2DL1 / Q000235:genetics*; D014184:Transplantation, Homologous
chemical_list: D015236:HLA-C Antigens; C093100:KIR2DL1 protein, human; D054342:Receptors, KIR2DL1; D001120:Arginine; D003545:Cysteine
references.citation: Blood. 2009 Dec 10;114(25):5182-90
references.pmid: 19828694
references.citation: Br J Haematol. 2011 Oct;155(1):14-29
references.pmid: 21812770
references.citation: Immunogenetics. 2010 Jul;62(7):431-40
references.pmid: 20454893
references.citation: J Exp Med. 2006 Mar 20;203(3):633-45
references.pmid: 16533882
references.citation: Tissue Antigens. 2007 Nov;70(5):415-22
references.pmid: 17854430
references.citation: Blood. 2008 Sep 15;112(6):2369-80
references.pmid: 18583565
references.citation: Blood. 1999 Jul 1;94(1):333-9
references.pmid: 10381530
references.citation: J Leukoc Biol. 2011 Oct;90(4):703-16
references.pmid: 21873457
references.citation: Philos Trans R Soc Lond B Biol Sci. 2012 Mar 19;367(1590):800-11
references.pmid: 22312047
references.citation: Hum Immunol. 2001 Apr;62(4):399-407
references.pmid: 11295473
references.citation: Blood. 2011 Jan 20;117(3):764-71
references.pmid: 20889923
references.citation: Blood. 2009 Mar 26;113(13):3119-29
references.pmid: 18945967
references.citation: Hum Immunol. 2007 May;68(5):309-23
references.pmid: 17462498
references.citation: Blood. 2010 Oct 7;116(14):2411-9
references.pmid: 20581313
references.citation: Nature. 2005 Aug 4;436(7051):709-13
references.pmid: 16079848
references.citation: Pediatr Transplant. 2011 Mar;15(2):198-204
references.pmid: 21309963
references.citation: N Engl J Med. 2012 Aug 30;367(9):805-16
references.pmid: 22931314
references.citation: J Immunol. 2003 Dec 15;171(12):6640-9
references.pmid: 14662867
references.citation: Tissue Antigens. 2007 Mar;69(3):250-4
references.pmid: 17493149
references.citation: Leukemia. 2005 Aug;19(8):1446-51
references.pmid: 15973456
references.citation: Blood. 2009 Jan 15;113(3):726-32
references.pmid: 18945962
references.citation: Immunol Rev. 2006 Dec;214:155-60
references.pmid: 17100883
references.citation: Transplant Proc. 2006 Jan-Feb;38(1):287-91
references.pmid: 16504727
references.citation: Science. 2002 Mar 15;295(5562):2097-100
references.pmid: 11896281
references.citation: Hum Immunol. 2002 Apr;63(4):271-80
references.pmid: 12039408
references.citation: Blood. 2010 May 27;115(21):4293-301
references.pmid: 20233969
references.citation: Bone Marrow Transplant. 2012 Jun;47(6):817-23
references.pmid: 22139069
references.citation: Curr Opin Hematol. 2012 Jul;19(4):319-23
references.pmid: 22555394
references.citation: Blood. 2011 Jul 14;118(2):223-30
references.pmid: 21613256
references.citation: Biol Blood Marrow Transplant. 2006 Aug;12(8):828-36
references.pmid: 16864053
references.citation: Immunity. 2011 Nov 23;35(5):653-7
references.pmid: 22118518
references.citation: Immunity. 2006 Aug;25(2):331-42
references.pmid: 16901727
references.citation: Blood. 2006 Feb 1;107(3):1238-9
references.pmid: 16434496
references.citation: Eur J Immunol. 2007 Jan;37(1):199-211
references.pmid: 17171757
references.citation: Br J Haematol. 2005 Nov;131(4):483-6
references.pmid: 16281939
references.citation: Immunogenetics. 2008 Nov;60(11):655-67
references.pmid: 18682925
references.citation: J Immunol. 2005 May 15;174(10):6540-5
references.pmid: 15879158
references.citation: PLoS One. 2010 Dec 29;5(12):e15115
references.pmid: 21206914
references.citation: Transplantation. 2006 Oct 27;82(8):1024-30
references.pmid: 17060849
references.citation: Tissue Antigens. 2008 Oct;72(4):383-91
references.pmid: 18643963
references.citation: Blood. 2005 Jun 15;105(12):4878-84
references.pmid: 15731175
references.citation: Immunol Rev. 2002 Dec;190:40-52
references.pmid: 12493005
references.citation: Nat Rev Immunol. 2013 Feb;13(2):133-44
references.pmid: 23334245
references.citation: J Immunol. 2004 Jan 1;172(1):644-50
references.pmid: 14688377
references.citation: Blood. 2009 Apr 16;113(16):3875-84
references.pmid: 19179302
references.citation: Blood. 2007 Jun 1;109(11):5058-61
references.pmid: 17317850
references.citation: Clin Immunol. 2011 Mar;138(3):274-81
references.pmid: 21239231
references.citation: Nat Genet. 2007 Sep;39(9):1114-9
references.pmid: 17694058