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-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), 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-alpha was correlated with TGF-beta (P =.001) and with monocyte/macrophage cells (P =.003). Patients with excess blasts in their marrows had a higher TGF-beta level (P =.01) and monocyte/macrophage number (P =.05). In a linear regression model, TGF-beta 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-alpha, TGF-beta 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. (C) 2002 The Japanese Society of Hematology.