Cytidine Deaminase Genetic Variants Influence RNA Expression and Cytarabine Cytotoxicity in Acute Myeloid Leukemia

Abstract

CDA genetic variants explain the variation in RNA expression and may be candidates for individualizing Ara-C therapy.

Variants inCDAandABCB1are predictors of capecitabine-related adverse reactions in colorectal cancer

“…CDA plays an important role in the conversion of capecitabine to 5-FU, and variants in this gene have been related to capecitabine-induced toxicity [11, 22, 30]. CDA 79A>C has been associated with CDA activity and with toxicity to cytarabine, which is also metabolized by CDA [31, 32]. In contrast to our findings, those of other studies did not show a connection between this SNP and toxicity induced by capecitabine [11, 22] and fluoropyrimidines [33].…”

RNA Expression of Genes Involved in Cytarabine Metabolism and Transport Predicts Cytarabine Response in Acute Myeloid Leukemia

“…Among all the candidate genes, CDA expression showed maximum fold variation in this study (Supplementary Figure 2). This variation in expression could be attributed to the highly polymorphic nature of CDA gene [24], and many of these polymorphisms have been shown to influence treatment outcome [40,41]. CDA expression was found to be significantly lower in patients who were sensitive to Ara-C when compared with those resistant ex vivo (IC50 > 6 μM).…”

“…Ex vivo cytotoxicity of Ara-C was determined using the MTT assay, as described previously [24]. Briefly, bone marrow mononuclear cells (BMMNCs) were isolated using Ficoll-paque (GE Healthcare, CA, USA) and 1 × 10 5 cells were cultured in flat-bottomed 96-well Research Article Abraham, Varatharajan, Karathedath et al microtiter plates in the presence of increasing concentrations of Ara-C (cytosine β-D-arabinofuranoside hydrochloride (Ara-C HCl; Sigma-Aldrich, MO, USA), ranging from 0.1 to 80.0 μM for 48 h. IC50 values were calculated using ADAPT 5 software [25].…”

SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study

“…CDA may be another factor for Ara-C resistance. Elevated CDA activity was correlated with Ara-C resistance [33,50]. CDA could be an independent prognostic parameter for survival in AML patients treated with Ara-C [27].…”