By Domenico Ribatti
It has been as a rule approved that angiogenesis is desirous about the pathogenesis of hematological malignancies, like acute and persistent leukemia, lymphoma, myelodysplastic syndromes, myeloproliferative neoplasms and a number of myeloma. the level of angiogenesis within the bone marrow has been correlated with ailment burden, diagnosis and therapy final result. Reciprocal confident and adverse interactions among tumor cells and bone marrow stromal cells, specifically hematopoietic stem cells, fibroblasts, osteoblasts/osteoclasts, endothelial cells, endothelial progenitor cells, T cells, macrophages and mast cells, mediated through an array of cytokines, receptors and adhesion molecules, modulate the angiogenic reaction in hematological tumors. extra lately, it's been emphasised the pro-angiogenic position of the so referred to as “vascular niche”, indicating a domain wealthy in blood vessels the place endothelial cells and mural cells reminiscent of pericytes and tender muscle cells create a microenvironment that has effects on the habit of numerous stem and progenitor cells, in hematological malignancies.
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Genetic depletion of this subpopulation of CD68+ VEGFR1+ myelo-monocytic cells was sufficient to inhibit angiogenesis in various tumor experimental models, including lymphoma (De Palma et al. 2003). 6 The Role of Macrophages and Mast Cells Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B cell NHL, suggesting that an increase number of macrophages may be recruited and activated locally by malignant B cells, and that angiogenesis associated with B cell-NHL may be induced, at least, partly, by angiogenic factors secreted by macrophages (Vacca et al.
Nuclear factor kB (NFkB) is a transcription factor known to affect the expression of several chemokines and it has been demonstrated that bortezomib, a proteasome inhibitor that inhibits NFkB activation decreases CCL2 and CCL4 levels (Bruserud et al. 2007). In this context, 54 4 Angiogenesis in Leukemia the chemokine system may be considered as a possible therapeutic target and chemokine inhibitors used as a class of drugs that may become important for inhibition of angiogenesis in leukemias (Melve et al.
2009). 4 Angiogenesis in Acute and Chronic Myeloid Leukemia … 53 Fig. 1 Angiogenic activity of supernatants from two acute myeloid leukemia cell lines, U937 ( upper panels) or K562 ( lower panels), cultured in the absence ( left panels) or presence ( right panels) of rhIL-12, as assessed by the in vivo CAM assay. (Reproduced from Ferretti et al. 2010) Hussong et al. (2000) found significantly increased MVD in the bone marrow of AML patients and higher MVD predicted for poor prognosis (Kuzu et al.