title: Yin and yang of cytidine deaminase roles in clinical response to azacitidine in the elderly: a pharmacogenetics tale.
abstract: Azacitidine is a mainstay for treating hematological disorders. Azacitidine is metabolized by cytidine deaminase, coded by a highly polymorphic gene. Here, we present two elderly patients with opposite clinical outcomes after azacitidine treatment. First, an acute myeloid leukemia patient showed life-threatening toxicities, but outstanding complete remission, after a single round of azacitidine. Further investigations showed that this patient was cytidine deaminase 79A>C (rs2072671) homozygous with a marked deficient phenotype. Next, a chronic myelomonocytic leukemia patient displayed complete lack of response despite several cycles of azacitidine. This patient had a rapid-deaminator phenotype linked to the -31delC deletion (rs3215400). These polymorphisms lead to opposite clinical outcomes in patients with myelodysplastic syndromes treated with azacitidine, thus suggesting that determining cytidine deaminase status could help to forecast clinical outcome.
authors.affiliation: SMARTc Unit, Pharmacokinetics Laboratory, UMR_911 CRO2 AMU Marseille, France.|Pharmacy Unit, La Conception University Hospital of Marseille, APHM, Marseille, France.
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Fanciullino
authors.affiliation: Onco-Hematology Unit, La Conception University Hospital of Marseille, APHM, Marseille, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Mercier
authors.affiliation: SMARTc Unit, Pharmacokinetics Laboratory, UMR_911 CRO2 AMU Marseille, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Serdjebi
authors.affiliation: Onco-Hematology Unit, La Conception University Hospital of Marseille, APHM, Marseille, France.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Venton
authors.affiliation: Onco-Hematology Unit, La Conception University Hospital of Marseille, APHM, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Colle
authors.affiliation: Transfer Oncology Laboratory, Nord University Hospital of Marseille, APHM, Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fina
authors.affiliation: Transfer Oncology Laboratory, Nord University Hospital of Marseille, APHM, Marseille, France.
authors.forename: L'Houcine
authors.initials: L
authors.lastname: Ouafik
authors.affiliation: SMARTc Unit, Pharmacokinetics Laboratory, UMR_911 CRO2 AMU Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
authors.affiliation: SMARTc Unit, Pharmacokinetics Laboratory, UMR_911 CRO2 AMU Marseille, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ciccolini
authors.affiliation: Onco-Hematology Unit, La Conception University Hospital of Marseille, APHM, Marseille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Costello
mesh_terms: D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001374:Azacitidine / Q000009:adverse effects*; D003564:Cytidine Deaminase / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*
chemical_list: D000964:Antimetabolites, Antineoplastic; D003564:Cytidine Deaminase; D001374:Azacitidine
keywords: azacitidine; cytidine deaminase; efficacy; genetic polymorphism; myelodysplastic syndromes; toxicity