Analysis of Clinical Impact of CD33 rs12459419 Single-Nucleotide Polymorphism in AML Treated with Intensive Chemotherapy Without Gemtuzumab Ozogamicin

The CD33 rs12459419 (C>T; Ala14Val) single-nucleotide polymorphism (SNP) has been reported to modulate treatment response and survival in pediatric patients with acute myeloid leukemia (AML) receiving gemtuzumab ozogamicin (GO), an anti-CD33 antibody linked to the cytotoxic compound calicheamicin. However, it remains unclear whether this SNP also affects CD33 expression on leukemic blasts. Moreover, its prognostic significance in adult AML patients treated with standard chemotherapy without GO has not been investigated. In this study, we retrospectively genotyped 184 adult AML patients who received standard induction chemotherapy for the CD33 rs12459419 SNP genotype and collected CD33 expression data. The observed genotype distribution was 46% (n = 85) CC, 43% (n = 79) CT, and 11% (n = 20) TT. CD33 expression was detected in significantly higher proportions of leukemic blasts in patients with the CC genotype than those with the TT genotype (p = 0.0009). A similar trend was observed between the CT and TT genotypes (p = 0.06). No significant differences in clinical outcome were detected among the three genotype cohorts. Grouping CC and CT genotypes together based on their similar CD33 expression and comparing them to patients with the TT genotype also revealed no differences in overall survival (OS), event-free survival (EFS), or relapse-free survival (RFS). Using a proportion of 90% CD33-positive blasts to define high versus low expression groups also failed to identify a meaningful impact on OS, EFS, or RFS, either across genotypes or independent of genotype. In conclusion, our findings indicate that the CD33 rs12459419 SNP does not affect outcomes or survival in adult AML patients receiving standard chemotherapy in the absence of GO. Furthermore, no association was seen between CD33 expression and clinical outcomes between the three genotypes. To our knowledge, this is the first study to investigate the prognostic impact of the CD33 rs12459419 SNP per se on outcome and survival in adult AML patients treated with chemotherapy without GO. Validation in larger patient cohorts is required to conclusively rule out a prognostic role of the CD33 rs12459419 SNP in AML.