Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases

Mingjiang Xu, Edward Bruno, Joseph Chao, Stephen Huang, Guido Finazzi, Steven M. Fruchtman, Uday Popat, Josef T. Prchal, Giovanni Barosi, Ronald Hoffman

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Idiopathic myelofibrosis (IM) is characterized by increased numbers of CD34+ cells in the peripheral blood (PB). We explored the possible mechanisms underlying this abnormal trafficking of CD34+ cells. Plasma levels of neutrophil elastase (NE), total and active matrix metalloproteinase 9 (MMP-9), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were dramatically increased in IM. The absolute number of CD34 + cells in the PB was correlated with the levels of sVCAM-1. Marked elevations of the levels of NE but not total and active MMP-9 as well as MMP-2 were detected in media conditioned by IM mononuclear cells (MNCs) as compared with that of healthy volunteers. IM MNC-conditioned media, however, was shown by zymographic analysis to contain increased gelatinolytic activity corresponding to the molecular weight of MMP-9. IM MNC-conditioned media also exhibited a greater ability to cleave VCAM-1 and c-kit in vitro, consistent with the biologic actions of NE. In addition, the increased ability of IM PB CD34 + cells to migrate through a reconstituted basement membrane was diminished by several inhibitors of MMP-9 activity, indicating that these cells express increased levels of this MMP. These data indicate that a proteolytic environment exists in IM which might result in the sustained mobilization of CD34+ cells.

Original languageEnglish (US)
Pages (from-to)4508-4515
Number of pages8
JournalBlood
Volume105
Issue number11
DOIs
StatePublished - Jun 1 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Xu, M., Bruno, E., Chao, J., Huang, S., Finazzi, G., Fruchtman, S. M., Popat, U., Prchal, J. T., Barosi, G., & Hoffman, R. (2005). Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases. Blood, 105(11), 4508-4515. https://doi.org/10.1182/blood-2004-08-3238