Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis

Stefan O. Ciurea, Delwin Merchant, Nadim Mahmud, Takefumi Ishii, Yan Zhao, Wenyang Hu, Edward Bruno, Giovanni Barosi, Mingjiang Xu, Ronald Hoffman

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

In order to investigate the biologic processes underlying and resulting from the megakaryocytic hyperplasia that characterizes idiopathic myelofibrosis (IMF), peripheral blood CD34+ cells isolated from patients with IMF, polycythemia vera (PV), and G-CSF-mobilized healthy volunteers were cultured in the presence of stem cell factor and thrombopoietin. IMF CD34+ cells generated 24-fold greater numbers of megakaryocytes (MKs) than normal CD34 + cells. IMF MKs were also shown to have a delayed pattern of apoptosis and to overexpress the antiapoptotic protein bcl-xL. MK hyperplasia in IMF is, therefore, likely a consequence of both the increased ability of IMF progenitor cells to generate MKs and a decreased rate of MK apoptosis. Media conditioned (CM) by CD61+ cells generated in vitro from CD34 + cells were then assayed for the levels of growth factors and proteases. Higher levels of transforming growth factor-β (TGF-β) and active matrix metalloproteinase-9 (MMP9) were observed in media conditioned with IMF CD61+ cells than normal or PV CD61+ cells. Both normal and IMF CD61+ cells produced similar levels of VEGF. MK-derived TGF-B and MMP-9, therefore, likely contribute to the development of many pathological epiphenomena associated with IMF.

Original languageEnglish (US)
Pages (from-to)986-993
Number of pages8
JournalBlood
Volume110
Issue number3
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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Primary Myelofibrosis
Megakaryocytes
Transforming Growth Factors
Conditioned Culture Medium
Apoptosis
Thrombopoietin
Stem Cell Factor
Matrix Metalloproteinase 9
Granulocyte Colony-Stimulating Factor
Matrix Metalloproteinases
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Blood
Peptide Hydrolases
Polycythemia Vera
Proteins
Hyperplasia
Blood Cells
Healthy Volunteers
Stem Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Ciurea, S. O., Merchant, D., Mahmud, N., Ishii, T., Zhao, Y., Hu, W., ... Hoffman, R. (2007). Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. Blood, 110(3), 986-993. https://doi.org/10.1182/blood-2006-12-064626

Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. / Ciurea, Stefan O.; Merchant, Delwin; Mahmud, Nadim; Ishii, Takefumi; Zhao, Yan; Hu, Wenyang; Bruno, Edward; Barosi, Giovanni; Xu, Mingjiang; Hoffman, Ronald.

In: Blood, Vol. 110, No. 3, 01.08.2007, p. 986-993.

Research output: Contribution to journalArticle

Ciurea, SO, Merchant, D, Mahmud, N, Ishii, T, Zhao, Y, Hu, W, Bruno, E, Barosi, G, Xu, M & Hoffman, R 2007, 'Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis', Blood, vol. 110, no. 3, pp. 986-993. https://doi.org/10.1182/blood-2006-12-064626
Ciurea SO, Merchant D, Mahmud N, Ishii T, Zhao Y, Hu W et al. Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. Blood. 2007 Aug 1;110(3):986-993. https://doi.org/10.1182/blood-2006-12-064626
Ciurea, Stefan O. ; Merchant, Delwin ; Mahmud, Nadim ; Ishii, Takefumi ; Zhao, Yan ; Hu, Wenyang ; Bruno, Edward ; Barosi, Giovanni ; Xu, Mingjiang ; Hoffman, Ronald. / Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. In: Blood. 2007 ; Vol. 110, No. 3. pp. 986-993.
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