transforming-growth-factor-beta and Leukemia--Myelomonocytic--Chronic

The myelodysplastic syndromes are a heterogeneous group of clonal diseases of haemopoiesis, which are a challenge for both biologists and clinicians. In this paper the current classification and the recent advances in the understanding the disease mechanisms are reviewed. The recent therapeutic advances are also indicated, such as intensive and low-dose chemotherapy, new drugs, erythropoietin and colony-stimulating factors. However, the work has been focused on thalidomide, its therapeutic potential, its modes of actions, side effects, indications and future applications.

Topics: Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Antineoplastic Agents; Chromosome Aberrations; Constipation; Cytokines; Dyspnea; Fatigue; Humans; Immunosuppressive Agents; Interleukin-1; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Thalidomide; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

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.

Topics: Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Animals; Apoptosis; Bone Marrow Cells; Cell Division; Cytokines; Female; Humans; Leukemia, Myelomonocytic, Chronic; Macrophages; Male; Monocytes; Myelodysplastic Syndromes; Regression Analysis; S Phase; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha