title: NK cell genotype and phenotype at diagnosis of acute lymphoblastic leukemia correlate with postinduction residual disease.
abstract: OBJECTIVE
  Not all natural killer (NK) cells are equally cytotoxic against leukemia because of differences in receptor gene content and surface expression. We correlated NK cell genotype and phenotype at diagnosis of childhood acute lymphoblastic leukemia (ALL) with minimal residual disease (MRD) after induction chemotherapy.
  
  
  METHODS
  The NK cells and leukemia blasts of 244 patients were analyzed at diagnosis by killer-cell immunoglobulin-like receptor (KIR) typing and immunophenotyping. The results were correlated statistically with postinduction MRD status.
  
  
  RESULTS
  The odds of being MRD positive in patients with KIR telomeric (Tel)-A/B genotype were 2.85 times the odds in those with Tel-A/A genotype (P = 0.035). MRD-positive patients were more likely to have KIR2DL5A (P = 0.006) and expressed less activating receptor NKp46 and FASL on their NK cells (P = 0.0074 and P = 0.029, respectively). The odds of being MRD positive increased by 2.01-fold for every percentage increase in NK cells expressing KIR2DL1 in the presence of HLA-C2 ligand (P = 0.034). The quantity of granzyme B inhibitor PI-9 in the leukemia blasts was greater in patients who were MRD positive (P = 0.038). Collectively, five NK cell-related factors (Tel-B-associated KIR2DL5A, NKp46, FASL, granzyme B, and PI-9) are strongly associated with MRD positivity at the end of induction with 100% sensitivity and 80% specificity.
  
  
  CONCLUSIONS
  Our data support the hypothesis that NK cells with a strong effector phenotype in the setting of decreased leukemia resistance are associated with better leukemia control.
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Sullivan
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Guolian
authors.initials: G
authors.lastname: Kang
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rooney
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Martha
authors.initials: M
authors.lastname: Holladay
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Rafijul
authors.initials: R
authors.lastname: Bari
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schell
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: MaCal
authors.initials: M
authors.lastname: Tuggle
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee. University of Tennessee Health Science Center, Memphis, Tennessee. Wing.Leung@stjude.org.
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D018365:Neoplasm, Residual / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D054340:Receptors, KIR / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell