Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
TGF-β1 induces bone marrow reticulin fibrosis in hairy cell leukemia
Medhat Shehata, … , Markus Duechler, Heinz Gisslinger
Medhat Shehata, … , Markus Duechler, Heinz Gisslinger
Published March 1, 2004
Citation Information: J Clin Invest. 2004;113(5):676-685. https://doi.org/10.1172/JCI19540.
View: Text | PDF
Article Hematology

TGF-β1 induces bone marrow reticulin fibrosis in hairy cell leukemia

  • Text
  • PDF
Abstract

The mechanisms that lead to reticulin fibrosis of bone marrow (BM) in hairy cell leukemia (HCL) are not fully understood. We therefore investigated the involvement of TGF-β1, a potent fibrogenic cytokine, in this process. Immunoassays revealed that TGF-β1 is present at higher concentrations in BM, serum, and plasma of HCL patients in comparison with healthy donors (P < 0.001). RT-PCR and immunofluorescence studies showed that TGF-β1 is overexpressed at the mRNA and protein levels in peripheral blood, spleen, and BM mononuclear cells and that hairy cells (HCs) are the main source of TGF-β1. Active TGF-β1 correlated significantly with grades of BM fibrosis, infiltration with HCs, and serum procollagen type III aminoterminal propeptide (PIIINP). Ex vivo studies demonstrated that TGF-β1 significantly enhances the production and deposition of reticulin and collagen fibers by BM fibroblasts. In addition, BM plasma of HCL patients increased the synthesis of type I and type III procollagens, the main components of reticulin fibers, at the mRNA and protein levels. This fibrogenic activity of BM plasma was abolished by neutralizing anti–TGF-β1 antibodies. These results show, for the first time to our knowledge, that TGF-β1 is highly expressed in HCs and is directly involved in the pathogenesis of BM reticulin fibrosis in HCL.

Authors

Medhat Shehata, Josef D. Schwarzmeier, Martin Hilgarth, Rainer Hubmann, Markus Duechler, Heinz Gisslinger

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Levels of TGF-β1 in BMP, serum, and PBP. TGF-β1 was measured by immunoas...
Levels of TGF-β1 in BMP, serum, and PBP. TGF-β1 was measured by immunoassays before and after acidification to detect active (A) and total (B) TGF-β1. The levels of active and total TGF-β1 were significantly higher in HCL patients (n = 13) than in HDs (n = 10) and B-CLL patients (n = 5). *P < 0.01; **P < 0.001. (C) High expression of TGF-β1 mRNA in PBMCs of HCL patients (lanes 7–12) in comparison with HDs (lanes 1–6). (D) Overexpression of TGF-β1 mRNA in BMMCs of three HCL patients and spleen (spl.) cells of two HCL patients compared with BMMCs of three HDs and PBMCs (lanes 9 and 10) and BMMCs (lanes 11 and 12) of B-CLL patients.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts