Cancer

Patient sample, cell culture and mouse studies identified an inhibitor of PRMT5 histone methyltransferase activity that could help treat CML. In patient CD34⁺ hematopoietic stem cells from peripheral blood and in patient bone marrow samples, levels of PMRT5 were higher than in bone marrow samples from healthy volunteers. In vitro screening of a small molecule library identified a compound that inhibited the histone methyltransferase activity of PRMT5 with an IC₅₀ of 0.5 μM. In CD34⁺ leukemic stem cells from patients, the compound decreased colony formation and increased apoptosis compared with vehicle. In a mouse model of CML, the compound decreased splenomegaly and the numbers of leukemia stem cells in bone marrow and spleen and increased survival. Next steps could include optimizing and testing the compound in xenograft mouse models of CML...