Purpose
Purpose of this study was to evaluate clinical implications of CD33 SNPs in pediatric acute myeloid leukemia (AML) patients 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) from remission was 84±8% for those homozygous (GG) for rs35112940 vs. 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 have favorable-risk disease as compared CC and CT genotypes (52% vs. 31%, p=0.034) and significantly lower diagnostic blast CD33 expression as compared to other genotypes (p<0.001).
Conclusion
Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric AML.
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