Biological Significance of Proliferation, Apoptosis, Cytokines, and Monocyte/Macrophage Cells in Bone Marrow Biopsies of 145 Patients With Myelodysplastic Syndrome
Labeling index (LI), apoptosis, levels of 2 pro-apoptotic cytokines tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and the number of monocyte/macrophage cells that are the likely source of the cytokines were simultaneously measured in plastic-embedded bone marrow (BM) biopsy sections of 145 patients with myelodysplastic syndromes (MDS). TNF-α was correlated with TGF-β (P = .001) and with monocyte/macrophage cells (P = .003). Patients with excess blasts in their marrows had a higher TGF-β level (P = .01) and monocyte/macrophage number (P = .05). In a linear regression model, TGF-β emerged as the most significant biological difference between patients who have excess of blasts and those who do not (P = .01). We conclude that in addition to TNF-α, TGF-β also plays a significant role in the initiation and pathogenesis of MDS, and that a more precise definition of its role will likely identify better preventive and therapeutic strategies.
Key wordsMyelodysplastic syndromes Cytokines Labeling index Apoptosis Tumor necrosis factor-α Transforming growth factor-β Monocyte/macrophage cells
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- 2.Wickramasinghe SN.Blood and Bone Marrow. 3rd ed. London, England: Churchill Livingstone; 1986.Google Scholar
- 4.Resegotti L. The nature and natural history of myelodysplasia.Haematologica. 1993;5:191–204.Google Scholar
- 17.Mundle S, Mativi BY, Bagai K, et al. Spontaneous down-regulation of Fas-associated phosphatase-1 (Fap-1) may contribute to the excessive apoptosis in myelodysplastic marrows.Int J Hematol. 1999;70:83–90.Google Scholar
- 18.Raza A, Venugopal P, Gezer S, et al. Pilot study of pentoxifylline and Ciprofloxacin with or without dexamethasone produces encouraging results in myelodysplastic syndromes. In: Hiddemann W, Buchner T, Wormann B, Ritter J, Creutzig U, Keating M, Plunkett W, eds.Acute Leukemias VII: Experimental Approaches and Novel Therapies. New York, NY: Springer-Verlag; 1998:42–51.CrossRefGoogle Scholar
- 32.Shetty V, Hussaini S, Broady-Robinson L, Allampallam K, et al. Intramedullary apoptosis of hematopoietic cells in myelodysplastic syndrome patients can be massive: apoptotic cells recovered from high density fraction of bone marrow aspirates.Blood. 2000;96:1388–1392.PubMedPubMedCentralGoogle Scholar
- 33.Alvi S, Borok R, Showel M, et al. Formation of large molecular weight DNA fragments may be a committed step of apoptosis in myelodysplastic syndromes vs acute myeloid leukemia [abstract].Proc Am Assoc Cancer Res. 1996;37:Abstract 185.Google Scholar