Spleen neoangiogenesis in patients with myelofibrosis with myeloid metaplasia

Neoangiogenesis is an integral component of bone marrow myeloproliferation in patients with myelofibrosis with myeloid metaplasia (MMM). As extramedullary haematopoiesis is a constitutive feature of MMM, we studied spleen neoangiogenesis by a computerized image analysis in MMM patients. Compared with five normal subjects, spleen CD34-staining capillary vascular density (CVD) was 2.1-3.03 times higher than the upper range of normal in six of the 15 (40%) MMM patients. CD8-staining sinusoidal vascular density (SVD) was constantly normal or lesser than normal and was inversely correlated with CVD (R=-0.53; P=0.04). In MMM patients who did not receive cytoreductive or radiation therapy in the month before splenectomy (n=9), the CVD was a significant determinant of spleen size (R=0.88; P=0.04). In MMM patients, the number of spleen CD34(+) haematopoietic stem cells was increased from 1.2 to 98 times the upper limit of normal, and predicted the expansion of CVD (R=0.57; P=0.03). A population of cells expressing the CD34(+)/CD133(+)/VEGFR-2(+) angiopoietic phenotype was present in the blood and spleen of five of seven patients. These results document that neoangiogenesis is an integral component of spleen re-localization of haematopoietic stem cells and suggest a cellular mechanism for spleen neoangiogenesis.