The Impact of the Epigenetic Cancer Drug Azacitidine on Host Immunity: The Role of Myelosuppression, Iron Overload and tp53 Mutations in a Zebrafish Model.

ABSTRACT: The unsatisfactory real-world efficacy of the hypomethylating agent azacitidine in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has prompted us to investigate the hematological adverse events and host variables that may compromise the use of this epigenetic drug. Using the zebrafish, we found that azacitidine destroyed their myeloid precursors and impaired myeloid function by inhibiting antigen processing, allogeneic response and phagocytic activity, resulting in increased susceptibility to infection even by the normal flora E. coli. In addition, iron overload, a MDS-associated condition following repeated transfusions, exacerbated bacterial infection especially by V. vulnificus with known iron dependence. Furthermore, we show that the tp53M214K mutant zebrafis

SUBMITTER: Wang SC 

PROVIDER: S-EPMC6770285 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature