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De novo acute myeloid leukemia with normal karyotype (NK‐AML) comprises a large group of patients with no common cytogenetic alterations and with a large variation in treatment response. Single‐nucleotide polymorphisms (SNPs) in genes related to the metabolism of the nucleoside analogue AraC, the backbone in AML treatment, might affect drug sensitivity and treatment outcome. Therefore, SNPs may serve as prognostic biomarkers aiding clinicians in individualized treatment decisions, with the aim of improving patient outcomes. We analyzed polymorphisms in genes encoding cytidine deaminase (CDA 79A>C rs2072671 and −451C>T rs532545), 5′‐nucleotidase (cN‐II 7A>G rs10883841), and deoxycytidine kinase (DCK 3′UTR 948T>C rs4643786) in 205 de novo NK‐AML patients. In FLT3‐internal tandem duplication (ITD)‐positive patients, the CDA 79C/C and −451T/T genotypes were associated …