Transcription profiling by array of the effect of S78454, a pan histone deacetylase inhibitor, on megakaryopoiesis derived from human CD34+ cells

ABSTRACT: S78454 (Abexinostat, PCI-24781) is a pan histone deacetylase inhibitor (HDACi) that demonstrates efficacy in malignancy treatment. Like other HDACi, this drug induces a profound thrombocytopenia, whose mechanism is partially understood. We have tested its effect at doses reached in patients plasma on in vitro megakaryopoiesis derived from human CD34+ cells. When added at day 0 in culture, S78454 inhibited CFU-MK growth, megakaryocyte (MK) proliferation and differentiation. This effect only required a short incubation period. When added later on (day 8), the compound induced a dose-dependent decrease (up to 10-fold) in proplatelet formation. Decreased proliferation was due to induction of apoptosis and was not related to a defect in TPO/MPL/JAK2 signaling. MK gene profiling revealed a silen

ORGANISM(S): Homo sapiens

SUBMITTER: Philippe DESSEN 

PROVIDER: E-MTAB-1180 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress