Targeting megakaryocytic-induced fibrosis in myeloproliferative neoplasms by AURKA inhibition

Targeting SHP2 phosphatase in Myeloproliferative Neoplasms

Megakaryocytic hyperplasia in myeloproliferative neoplasms is driven by disordered proliferative, apoptotic and epigenetic mechanisms.

AIMS Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal proliferative bone marrow diseases characterised by extensive megakaryocytic hyperplasia and morphological atypia. Despite knowledge of genomic defects, the pathobiological processes driving these megakaryocytic abnormalities in MPN remain poorly explained. We have explored the proliferative, apoptotic and epigenetic pr...

Targeting Rho Associated Kinases in Leukemia and Myeloproliferative Neoplasms

If ROCKs are going to be targeted as anti-leukemic agents either as a monotherapy or in combination with existing drugs, a better characterization of the relative contribution of ROCK1 and ROCK2 in disease progression is essential.

Dysregulation of the intrinsic apoptotic pathway mediates megakaryocytic hyperplasia in myeloproliferative neoplasms

AIMS Megakaryocyte expansion in myeloproliferative neoplasms (MPNs) is due to uncontrolled proliferation accompanied by dysregulation of proapoptotic and antiapoptotic mechanisms. Here we have investigated the intrinsic and extrinsic apoptotic pathways of megakaryocytes in human MPNs to further define the mechanisms involved. METHODS The megakaryocytic expression of proapoptotic caspase-8, ca...

JAK2 Inhibition: Reviewing a New Therapeutical Option in Myeloproliferative Neoplasms

JAK2 is a tyrosine kinase gene that plays an essential role in the development of normal haematopoiesis. Hyperactivation of JAK2 occurs in myeloproliferative neoplasms by different mechanisms. As a consequence, JAK2 inhibitors have been designed to suppress the cytokine signalling cascade caused by the constitutive activation of JAK2. In clinical trials, JAK2 inhibitors are efficient in decreas...