Measurement of apoptosis, proliferation and three cytokines in 46 patients with myelodysplastic syndromes

Vilasini Shetty, Suneel Mundle, Sairah Alvi, Margaret Showel, La Tanya Broady-Robinson, Saleem Dar, Raphael Borok, John Showel, Stephanie Gregory, Shelby Rifkin, Sefer Gezer, Agapi Parcharidou, Parameswaran Venugopal, Rohit Shah, Beatrice Hernandez, Mary Klein, Devena Alston, Erwin Robin, Carlos Dominquez, Azra Raza

Research output: Contribution to journalArticlepeer-review

Abstract

Extensive apoptosis or programmed cell death (PCD) of both hematopoietic (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysplastic syndromes (MDS) cancels the high birth-rate resulting in ineffective hematopoiesis and has been demonstrated as the probable basis for peripheral cytopenias in MDS by our group. It is proposed that factors present in the microenvironment are inducing apoptosis in all the cells whether stromal or parenchymal. To investigate this hypothesis further, bone marrow biopsies from 46 MDS patients and eight normal individuals were examined for the presence of three cytokines, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) and granulocyte macrophage-colony stimulating factor (GM-CSF) and one cellular component, macrophages, by the use of monoclonal antibodies immunohistochemically. Results showed the presence of TNF-α and TGF-β in 41/46 and 40/46 cases of MDS respectively, while only 15 cases showed the presence of GM-CSF. Further a significant direct relationship was found between the degree of TNF-α and the incidence of PCD (p = 0.0015). Patients who showed high PCD also had an elevated TNF-α level. Thus, the expression of high amounts of TNF-α and TGF-β and low amounts of the viability factor GM-CSF may be responsible for the high incidence of PCD leading to ineffective hematopoiesis in MDS. Future studies will be directed at attempting to reverse the lesion in MDS by using anti-TNF-α drugs such as pentoxifylline.

Original languageEnglish (US)
Pages (from-to)891-900
Number of pages10
JournalLeukemia Research
Volume20
Issue number11-12
DOIs
StatePublished - Nov 1 1996
Externally publishedYes

Keywords

  • Apoptosis and macrophages
  • Granulocyte macrophage-colony stimulating factor (GM-CSF)
  • Myelodysplastic syndrome
  • Transforming growth factor-beta (TGF-β)
  • Tumor necrosis factor-alpha (TNF-α)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Measurement of apoptosis, proliferation and three cytokines in 46 patients with myelodysplastic syndromes'. Together they form a unique fingerprint.

Cite this