Angiogenesis in Chronic Myeloproliferative Diseases

Abstract

Increased angiogenic activity has been demonstrated in myelofibrosis with myeloid metaplasia (MMM), chronic myeloid leukemia (CML), and essential thrombocythemia (ET) by both bone marrow microvessel density evaluation and measurement of circulating angiogenic factors. MMM is probably the disease with the more pronounced angiogenesis among myeloproliferative disorders but the significance of this finding remains speculative since the angiogenic activity is not correlated with any of the clinical and laboratory features of the disease. Circulating serum levels of angiogenic factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were found increased in MMM, CML and ET but the frequent thrombocytosis that accompanies these diseases could limit the interpretation of these data since platelets and megakaryocytes may be considered a major source at least for VEGF. However, CML patients treated with interferon were found to have lower VEGF and HGF levels than untreated or hydroxyurea-treated patients, thus suggesting a possible antiangiogenic mechanism of this drug. In addition, preliminary experiences with the antiangiogenic drug thalidomide have shown therapeutic activity in some myeloproliferative disorders.

Effect of allogeneic stem cell transplantation on bone marrow angiogenesis in chronic myelogenous leukemia

“…Previous studies have demonstrated the presence of increased bone marrow angiogenesis in patients with CML. [12][13][14][15] As in the other hematological malignancies with a similar finding, increased bone marrow angiogenesis appears to have prognostic value in CML, predicting both progression and survival. 14 Malignant cells in CML may have a direct role in the formation of these new blood vessels, and studies suggest that inhibition of angiogenesis may at least in part explain the mechanism of action of drugs used in CML.…”

Serum Vascular Endothelial Growth Factor Level in Patients With Hematological Malignancies

“…Recently, the fact that angiogenesis may have an important role in hematological malignancies has attracted considerable attention and this has lead to conducting of new studies regarding the role of neovascularization in adult and pediatric acute leukemia, chronic leukemia, myelodysplastic syndromes, lymphomas and multiple myeloma (6,(13)(14)(15)(16)(17)(18)(19). Although increased angiogenesis in solid hematological tumors such as lymphomas looks reasonable in the light of the pathogenesis underlying solid tumorinduced angiogenesis, it is difficult to answer the question why tumors like acute leukemia that are liquid in nature induce angiogenesis.…”

“…However, many studies have demonstrated increased angiogenesis and angiogenic factors in acute leukemia (6,(13)(14)(15)(16)(17)(18)(19).…”

Perfusion parameters analysis of the vertebral bone marrow in patients with Ph1− chronic myeloproliferative neoplasms (PhnegMPN): A dynamic contrast‐enhanced MRI (DCE‐MRI) study

“…It has been documented that ET manifests a mild increase in the number of vessels but not any severe variation from normal vascular structures (39). In addition, only a striking distention of vascular structures is noticed in PV, but not a significant increase in the number of vessels (12,39), as opposed to MF that exhibits an increased angiogenesis. Finally, although the number of patients is not high, there were clear statistical significant differences between patients with and without MF.…”