Bone marrow fibrosis in primary myelofibrosis: Pathogenic mechanisms and the role of TGF-β

Archana Agarwal, Kerry A. Morrone, Matthias Bartenstein, Zhizhuang Joe Zhao, Amit K. Verma, Swati Goel

Research output: Contribution to journalReview article

20 Scopus citations

Abstract

Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights into the complex pathogenesis of MPNs, the etiology of fibrosis is not well understood. Furthermore, since JAK2 inhibitors do not lead to reversal of fibrosis further understanding of the biology of fibrotic process is needed for future therapeutic discovery. Transforming growth factor beta (TGF-β) is implicated as an important cytokine in pathogenesis of bone marrow fibrosis. Various mouse models have been developed and have established the role of TGF-β in the pathogenesis of fibrosis. Understanding the molecular alterations that lead to TGF-β mediated effects on bone marrow microenvironment can uncover newer therapeutic targets against myelofibrosis. Inhibition of the TGF-β pathway in conjunction with other therapies might prove useful in the reversal of bone marrow fibrosis in PMF.

Original languageEnglish (US)
Article number5
JournalStem Cell Investigation
Volume2016
Issue numberFEB
DOIs
StatePublished - Feb 1 2016

Keywords

  • GATA-1
  • Primary myelofibrosis (PMF)
  • Thrombopoietin (TPO)
  • Transforming growth factor beta 1 (TGF-β1)

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics
  • Developmental Biology

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