The MPN-RC Structure

Thirteen different institutions are currently participating in the MPN-RC. Each institution has its own unique intellectual environment, clinical and research facilities.

Click on a Project or Core to view details

Discovery Science

Project 1

Molecular Pathogenesis and Therapy of Myeloproliferative Neoplasms

Discovery Science

Project 2

Defining the Role of Megakaryocyte Abnormalties in the Progression of Primary Myelofibrosis

Discovery Science

Project 3

Development of Strategies to Deplete Myelofibrosis Stem Cells

Discovery Science

Project 4

MPN-RC Clinical Consortium


Project 2: Defining the Role of Megakaryocyte Abnormalties in the Progression of Primary Myelofibrosis

Principal Investigator: John Crispino (PI), PhD Annarita Migliaccio (co-PI), PhD

Drs. John Crispino and Anna Rita Migliaccio will focus on impact of megakaryocytic hyperplasia, one of the histopathological hallmarks of the MPNs, on MF pathogenesis. They will investigate if bone marrow fibrosis and disease progression is driven by aberrant cytokine secretion by abnormal megakaryocytes that are dysregulated by reduced expression of GATA1. Studying the effects of GATA1 deficiency on megakaryocyte maturation and on cytokine secretion provides an opportunity to identify additional therapeutic targets. In addition, the effects of TGF-β, which is elaborated by MF megakaryocytes, on normal and MF HSCs and HPCs will be assessed. Data generated during the prior funding period have led to a clinical trial of a TGF-β receptor kinase inhibitor, galunisertib, (MPN-RC Clinical Trial 118) in patients with advanced forms of MF.

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