MEASUREMENT OF APOPTOSIS, PROLIFERATION AND 3 CYTOKINES IN 46 PATIENTS WITH MYELODYSPLASTIC SYNDROMES

Extensive apoptosis or programmed cell death (PCD) of both hematopoiet ic (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysp lastic syndromes (MDS) cancels the high birth-rate resulting in ineffe ctive hematopoiesis and has been demonstrated as the probable basis fo r peripheral cytopenias in MDS by our group. It is proposed that facto rs present in the microenvironment are inducing apoptosis in all the c ells whether stromal or parenchymal. To investigate this hypothesis fu rther, bone marrow biopsies from 46 MDS patients and eight normal indi viduals were examined for the presence of three cytokines, tumor necro sis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-bet a) and granulocyte macrophage-colony stimulating factor (GM-CSF) and o ne cellular component, macrophages, by the use of monoclonal antibodie s immunohistochemically. Results showed the presence of JNF-alpha and TGF-beta in 41/46 and 40/46 cases of MDS respectively, while only 15 c ases showed the presence of GM-CSF. Further a significant direct relat ionship was found between the degree of TNF-alpha and the incidence of PCD (p = 0.0015). Patients who showed high PCD also had an elevated T NF-alpha level. Thus, the expression of high amounts of TNF-alpha and TGF-beta and low amounts of the viability factor GM-CSF may be respons ible for the high incidence of PCD leading to ineffective hematopoiesi s in MDS. Future studies will be directed at attempting to reverse the lesion in MDS by using anti-TNF-alpha drugs such as pentoxifylline. C opyright (C) 1996 Elsevier Science Ltd