Abstract
The uncontrolled proliferation of malignant lymphoblasts is the pathobiological hallmark in B cell precursor-ALL (BCP-ALL). Identification of inhibitory growth factors is of great importance for the understanding of growth control of leukemic B cell precursors and the development of novel therapeutic approaches in BCP-ALL. The aim of our study was the analysis of the effect of TGF-β on cell survival and apoptosis of B cell precursors (BCP) from patients with acute lymphoblastic leukemia in vitro. Experiments were performed in a coculture system with cloned murine fibroblasts, which efficiently block spontaneous ex vivo apoptosis of BCP and thus allows the assessment of cytokine-induced growth inhibition. TGF-β significantly reduced cell viability of highly purified, FACS isolated CD10+/CD19+ leukemic BCP by a mean of 53% (P = 0.0001). The loss of cell viability was accompanied by a significant increase of apoptosis with a mean of 70% (P = 0.0028). The TGF-β effect was blocked specifically by a monoclonal anti-TGF-β antibody. Induction of apoptotic cell death by TGF-β was not accompanied by reduction of bcl-2 protein expression. TGF-β transcription was not detected in the leukemic pre-B cell line BLIN-1, but in the murine fibroblasts. The growth inhibitory effect of TGF-β was not restricted to leukemic BCP. The cytokine also increased apoptosis of normal, highly purified BCP by a mean of 58%. The data identify TGF-β as a potent growth inhibitory cytokine for leukemic BCP.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Buske, C., Becker, D., Feuring-Buske, M. et al. TGF-β inhibits growth and induces apoptosis in leukemic B cell precursors. Leukemia 11, 386–392 (1997). https://doi.org/10.1038/sj.leu.2400586
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2400586
Keywords
This article is cited by
-
Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?
Molecular and Cellular Pediatrics (2017)
-
Reduction of endogenous transforming growth factors β prevents ontogenetic neuron death
Nature Neuroscience (2000)