Bone marrow expression of vascular endothelial growth factor in myelofibrosis with myeloid metaplasia

The biologic relevance and prognostic impact of angiogenesis is being increasingly recognized in many solid tumors and hematologic malignancies including myelofibrosis with myeloid metaplasia (MMM). Many cytokines including vascular endothelial growth factor (VEGF) have been implicated for neoangiogenesis in MMM. However, the exact humoral basis remains to be elucidated. We examined the expression of VEGF by immunohistochemistry in a prospective cohort of 66 MMM patients, including six with cellular phase disease, and five normal controls. Contrary to most other hematologic malignancies, the distribution and intensity of staining for VEGF in bone marrow was similar between the MMM patients and controls. Interestingly, all six cellular phase patients displayed significantly increased VEGF expression. Thus, upregulation of angiogenic cytokines other than VEGF such as TGF-beta or loss of activity of an anti-angiogenic cytokine might be the dominant pathway of endothelial activation in MMM. However, VEGF might contribute to the process in the early stages of the disease.