INCB057643 Rebalances Bone Marrow in MPNs by Shifting Megakaryopoiesis Toward Erythropoiesis

Preclinical data using a patient-derived xenograft model and clinical analyses from MPN patients treated with INCB057643 demonstrated that this BET inhibitor reduces JAK2 V617F+ stem cells and dysplastic megakaryocytes, lowers inflammatory cytokines and fibrosis, and importantly increases erythroid progenitors and improves hemoglobin levels, indicating a normalization of bone marrow function.

These findings suggest that INCB057643 can effectively reprogram aberrant hematopoiesis in MPNs by curtailing pathogenic megakaryocyte expansion and promoting erythropoiesis, thereby addressing both marrow fibrosis and anemia.