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: Raphaelle Fanciullino, Cédric Mercier, Cindy Serdjebi, Geoffroy Venton, Julien Colle, Frédéric Fina, L'Houcine Ouafik, Bruno Lacarelle, Joseph Ciccolini, Régis Costello
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 16 Issue 17 Pg. 1907-12 (Nov 2015) ISSN: 1744-8042 [Electronic] England
• PMID: 26556583 (Publication Type: Case Reports, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Cytidine Deaminase
• Azacitidine

Topics

• Aged, 80 and over
• Antimetabolites, Antineoplastic (adverse effects)
• Azacitidine (adverse effects)
• Cytidine Deaminase (genetics)
• Hematologic Neoplasms (drug therapy, genetics)
• Humans
• Male
• Pharmacogenetics (methods)