TY - JOUR
T1 - Bone marrow fibrosis in primary myelofibrosis
T2 - Pathogenic mechanisms and the role of TGF-β
AU - Agarwal, Archana
AU - Morrone, Kerry
AU - Bartenstein, Matthias
AU - Zhao, Zhizhuang Joe
AU - Verma, Amit
AU - Goel, Swati
N1 - Publisher Copyright:
© Stem Cell Investigation. All rights reserved.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - GATA-1
KW - Primary myelofibrosis (PMF)
KW - Thrombopoietin (TPO)
KW - Transforming growth factor beta 1 (TGF-β1)
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U2 - 10.3978/j.issn.2306-9759.2016.02.03
DO - 10.3978/j.issn.2306-9759.2016.02.03
M3 - Review article
AN - SCOPUS:84994820139
SN - 2306-9759
VL - 2016
JO - Stem Cell Investigation
JF - Stem Cell Investigation
IS - FEB
M1 - 5
ER -