Spleen neoangiogenesis in patients with myelofibrosis with myeloid metaplasia


Giovanni Barosi, M.D., Laboratorio di Informatica Medica, IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy. E-mail: barosig@smatteo.pv.it


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.