Spleen neoangiogenesis in patients with myelofibrosis with myeloid metaplasia

Abstract

Summary 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.

Splenectomy produces a rapid but transient decrease of the frequency of circulating CD34+ haematopoietic progenitor cells in primary myelofibrosis

“…BM biopsies indicate that the extent of BM content of CD34 + cells inversely correlates with the number of circulating CD34 + HPCs in the late disease phase as if PB CD34 + cells originate from extramedullary organs, particularly from the spleen (Thiele & Kvasnicka, 2005). Supporting this, we documented that the number of CD34 + cells in the spleen is directly correlated with that of circulating CD34 + cells (Barosi et al, 2004). However, data indicating that the spleen is the origin of circulating CD34 + cells are still lacking.…”

The Effect of CXCL12 Processing on CD34+ Cell Migration in Myeloproliferative Neoplasms

“…Furthermore, the degradation product of CXCL12 produced by MMP-2 and MMP-9 (CXCL12; 5-67 aa sequence) was shown to be capable of reducing the chemoattractant capacity of full CXCL12, suggesting that this truncate might act as a receptor antagonist. The increased presence of PMF CD34 + cells at extramedullary sites, such as spleen and liver, could be due to the presence of intact CXCL12 at those sites (31,32). This possible explanation requires further investigation.…”

The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis

“…Such proliferation of SVECs likely culminates in the increased density of capillaries observed in MF spleens. 17 Unlike MF SVECs, LCs from MF spleens were characterized by significant mitochondrial dysfunction, decreased ATP biosynthesis, protein synthesis and catabolism, and cell death. It is possible that the elevated cellular stress associated with excessive RBC filtration and phagocytosis in MF spleens might led to this gene expression pattern.…”