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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: 3' Untranslated Regions, 5' Untranslated Regions, Adolescent, Adult, Aged, Base Sequence, Case-Control Studies, Cell Line, Tumor, Cytarabine, Cytidine Deaminase, Drug Resistance, Neoplasm, Female, Gene Expression, Haplotypes, Humans, Introns, Leukemia, Myeloid, Acute, Male, Middle Aged, Molecular Sequence Data, Polymorphism, Single Nucleotide, RNA, Messenger, U937 Cells, Young Adult.
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Do cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia? Context: Cytidine deaminase (CDA) irreversibly deaminates cytarabine (Ara-C), a key component of acute myeloid leukemia (AML) induction and consolidation therapy. CDA overexpression results in Ara-C resistance, while decreased expression is associated with toxicity. We evaluated factors influencing variation in CDA mRNA expression in adult AML patients and normal controls, and how they contributed to Ara-C cytotoxicity in AML cells. CDA mRNA expression in 100 de novo AML patients and 36 normal controls were determined using quantitative reverse-transcriptase PCR. Genetic variants in the CDA gene were screened by direct sequencing. IC₅₀ of Ara-C was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. CDA RNA expression as well as Ara-C IC₅₀ showed wide variation in AML samples and normal controls. Fourteen sequence variants were identified, three of which (-33delC, intron 2 TCAT repeat and the 3´untranslated region 816delC variants) showed significant association with RNA expression and the nonsynonymous coding variant 79A>C was associated with Ara-C cytotoxicity.
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CDA genetic variants explain the variation in RNA expression and may be candidates for individualizing Ara-C therapy. Final Decision: yes