The Prognostic Significance of Genetic Polymorphisms of Deoxycytidine Kinase and Cytidine Deaminase on the outcome of Adult Acute Myeloid Leukemia Patients with Cytarabine Based Chemotherapy

Cytarabine (Ara-C) is the mainstay of treatment of acute myeloid leukemia (AML), but still, drug resistance and treatment-related toxicities are the main causes of treatment failure. Single nucleotide polymorphisms (SNPs) of the key genes involved in the metabolic pathway of Ara-C have been reported to affect the clinical outcome, so we aimed to investigate the potential association of SNPs of deoxycytidine kinase [DCK] 201C>T (rs2306744), DCK 360C>G (rs377182313) and cytidine deaminase (CDA) 79A>C (rs2072671) genes in adult Egyptian AML patients with the outcome. Genotyping of the studied SNPs was tested using PCR- RFLP technique in 142 adult de novo AML patients who received standard induction chemotherapy based on cytarabine and doxorubicin (3+7 protocol). The median (range) age of our patients was 38 (20-60) years. The studied SNPs genotypes had no significant influence on treatment response on day 28 of induction therapy. DCK 201 heterozygous CT genotype, DCK 201-T allele, [DCK 201(CC)/DCK 360(CC)/CDA 79(AC)] combination as well as hepatological, nephrological, neurological and hematological toxicities were independent prognostic markers on the survival of our AML patients. Nucleophosmin mutation was associated with the poor prognostic variant DCK 201-T and CDA 79-A alleles. Fms-like tyrosine3 kinase internal tandem duplication (FLT3-ITD) mutation was associated with the wild AA genotype of CDA 79A>C polymorphism, while FLT3-tyrosine kinase domain (TKD) mutation was associated with variant DCK360-G allele. These findings support the idea that the studied SNPs can be used as prognostic markers helping in tailored treatment for AML patients.