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Yin and yang of cytidine deaminase roles in clinical response to azacitidine in the elderly: a pharmacogenetics tale.

Fanciullino R 1, 2 Mercier C 2 Serdjebi C 1 Venton G 2 Colle J 2 Fina F 3 Ouafik L 3, 4 Lacarelle B 1 Ciccolini J 1 Costello R. 2
1 SMARTc
CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
2 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
3 Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM]
4 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
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.
Keywords : azacitidine cytidine deaminase efficacy genetic polymorphism myelodysplastic syndromes toxicity
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Journal articles
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https://hal-amu.archives-ouvertes.fr/hal-01480104
Contributor : l'Houcine Ouafik Connect in order to contact the contributor
Submitted on : Wednesday, March 1, 2017 - 10:02:41 AM
Last modification on : Thursday, October 21, 2021 - 4:00:56 AM

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Fanciullino R, Mercier C, Serdjebi C, Venton G, Colle J, et al.. Yin and yang of cytidine deaminase roles in clinical response to azacitidine in the elderly: a pharmacogenetics tale.. Pharmacogenomics, Future Medicine, 2015, 16 (17), pp.1907-12. ⟨10.2217/pgs.15.135⟩. ⟨hal-01480104⟩

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