It is accepted that increased angiogenesis is important in the pathophysiology of solid tumors. However, some recent studies show that angiogenesis and angiogenic factors may be important in MDS and AML. Both disorders are associated with an increase in the vascularity in the bone marrow as well as increased levels of various angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, an-giogenin, platelet-derived growth factor, hepatocyte growth factor, epidermal growth factor, tumor necrosis factor-a, and transforming growth factor-p. The angiogenic factors may be secreted by the neoplastic cells and promote the growth proliferation of leukemic cells in an autocrine fashion. Blood levels of angiogenin and vascular endothelial factors are elevated in myelodysplastic syndromes and in acute myeloid leukemia. Again, as for apoptosis, the molecular basis of these observations is unknown.

Fig. 8.3 Diagram illustrating the RAS/MAPK signaling in JMML and the percentage of cases with mutations in the PTPN11 (encoding SHP ), NF1 and RAS genes

with a diminution in the level of apoptosis. The molecular basis for these observations is unknown. Hopefully, studies of apoptosis alongside gene expression studies will help elucidate this phenomenon.

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