CDK6 coordinates JAK2V617F mutant MPN via NF-{kappa}B and apoptotic networks

We describe a critical role for CDK6 in MPN evolution. The absence of Cdk6 ameliorates clinical symptoms and prolongs survival. The CDK6 protein interferes with 3 hallmarks of disease: besides regulating malignant stem cell quiescence, it promotes nuclear factor B (NF-B) signaling and contributes to cytokine production while inhibiting apoptosis. The effects are not mirrored by palbociclib, showing that the functions of CDK6 in MPN pathogenesis are largely kinase independent. Our findings thus provide a rationale for targeting CDK6 in MPN.

Source: Blood - April 10, 2019 Category: Hematology Authors: Uras, I. Z., Maurer, B., Nivarthi, H., Jodl, P., Kollmann, K., Prchal-Murphy, M., Milosevic Feenstra, J. D., Zojer, M., Lagger, S., Grausenburger, R., Grabner, B., Holly, R., Kavirayani, A., Bock, C., Gisslinger, H., Valent, P., Kralovics, R., Sexl, V. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research