title: Clinical significance of CD33 nonsynonymous single-nucleotide polymorphisms in pediatric patients with acute myeloid leukemia treated with gemtuzumab-ozogamicin-containing chemotherapy.
abstract: OBJECTIVE
  The purpose of this study was to evaluate clinical implications of CD33 single-nucleotide polymorphisms (SNP) in pediatric patients with acute myeloid leukemia (AML) treated with gemtuzumab-ozogamicin (GO)-based therapy.
  
  
  METHODS
  We genotyped four CD33 SNPs: rs35112940 (G>A; Arg304Gly), rs12459419 (C>T; Ala14Val), rs2455069 (A>G; Arg69Gly), and rs1803254 (G>C; 3'UTR) in pediatric patients undergoing induction chemotherapy containing GO (COG-AAML03P1 trial; n = 242) or not containing GO (St. Jude AML02 trial; n = 172).
  
  
  RESULTS
  CD33 SNPs were correlated significantly with clinical characteristics and treatment outcome. The coding SNPs, rs35112940 and rs12459419, were significantly associated with clinical endpoints in COG-AAML03P1 but not in the St. Jude AML02 trial. Specifically, among white patients in COG-AAML03P1, the 3-year overall survival (OS) rate from remission was 84% ± 8% for those homozygous (GG) for rs35112940 versus 68% ± 15% for the other genotypes (P = 0.018); these patients also had a lower relapse risk and superior disease-free survival. Likewise, patients homozygous for variant allele (TT) for rs12459419 were more likely to have favorable risk disease than CC and CT genotypes (52% vs. 31%, P = 0.034) and significantly lower diagnostic blast CD33 expression than other genotypes (P < 0.001).
  
  
  CONCLUSIONS
  Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric AMLs.
authors: Department of Hematology, PUMA-Institute of Personalized Medicine, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors: Leslie
authors: L
authors: Mortland
authors: Todd A
authors: TA
authors: Alonzo
authors: Roland B
authors: RB
authors: Walter
authors: Robert B
authors: RB
authors: Gerbing
authors: Amit K
authors: AK
authors: Mitra
authors: Jessica A
authors: JA
authors: Pollard
authors: Michael R
authors: MR
authors: Loken
authors: Betsy
authors: B
authors: Hirsch
authors: Susana
authors: S
authors: Raimondi
authors: Janet
authors: J
authors: Franklin
authors: Stanley
authors: S
authors: Pounds
authors: Xueyuan
authors: X
authors: Cao
authors: Jeffrey E
authors: JE
authors: Rubnitz
authors: Raul C
authors: RC
authors: Ribeiro
authors: Alan
authors: A
authors: Gamis
authors: Soheil
authors: S
authors: Meshinchi
authors: Jatinder K
authors: JK
authors: Lamba
mesh_terms: D000293:Adolescent; D000617:Aminoglycosides / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D000079982:Gemtuzumab; D056726:Genetic Association Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012307:Risk Factors; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab