Clinical significance of CD33 nonsynonymous single-nucleotide polymorphisms in pediatric patients with acute myeloid leukemia treated with gemtuzumab-ozogamicin-containing chemotherapy

Leslie Mortland, Todd A. Alonzo, Roland B. Walter, Robert B. Gerbing, Amit K. Mitra, Jessica A. Pollard, Michael R. Loken, Betsy Hirsch, Susana Raimondi, Janet Franklin, Stanley Pounds, Xueyuan Cao, Jeffrey E. Rubnitz, Raul C. Ribeiro, Alan Gamis, Soheil Meshinchi, Jatinder K. Lamba

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Purpose: 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. Experimental Design: 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). Conclusion: Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric AMLs.

Original languageEnglish (US)
Pages (from-to)1620-1627
Number of pages8
JournalClinical Cancer Research
Volume19
Issue number6
DOIs
StatePublished - Mar 15 2013

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