The BET Inhibitor, CPI-0610, Promotes Myeloid Differentiation in Myelofibrosis Patient Bone Marrow and Peripheral CD34+Hematopoietic Stem Cells
BLOOD(2020)
Abstract
Myelofibrosis (MF) is characterized by progressive bone marrow (BM) fibrosis resulting from aberrant megakaryopoeisis and expression of pro-inflammatory cytokines. These two processes, heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation, lead to myeloproliferation and cytopenias. CPI-0610 is a potent, selective and unique BET inhibitor under investigation in MF patients as monotherapy or in combination with ruxolitinib in the MANIFEST trial (NCT02158858). In ruxolitinib naïve and experienced MF patients, treatment with CPI-0610 monotherapy or in combination with ruxolitinib not only reduced spleen volume and symptoms, but also improved hemoglobin levels and overcame transfusion dependency in a subset of patients. To evaluate the effects of CPI-0610 on BM biology, correlative analyses were conducted using patient samples collected from the MANIFEST trial.
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Key words
promotes myeloid differentiation,myelofibrosis patient bone marrow,bet inhibitor,bone marrow,stem cells
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