Angiogenesis and vascular endothelial growth factor‐/receptor expression in myeloproliferative neoplasms: correlation with clinical parameters and JAK2‐V617F mutational status

Abstract

SummaryData on angiogenesis in the bone marrow of BCR‐ABL1‐negative myeloproliferative neoplasm (MPN) patients suggest an increase of the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression, but relations to the JAK2‐V617F status remain controversial. We performed immunohistochemical studies of MVD and VEGF‐expression in 100 MPN, including 24 essential thrombocythemia‐ (ET), 46 polycythemia vera‐ (PV), 26 primary myelofibrosis‐ (PMF), four myelodysplastic (MDS)/MPN‐ and 20 control reactive bone marrow cases, and correlated these findings with biological and clinical key data and the JAK2‐V617F status. We found significantly increased MVD, particularly that assessed by CD105, and VEGF expression in MPN compared to controls (PMF > PV > MDS/MPN > ET). We observed stronger association between CD105‐MVD and VEGF expression, fibrosis, and JAK2‐V617F mutant allele burden, compared to CD34‐MVD. MVD was strongly increased in MPN with high JAK2‐V617F mutant allele burden. Our study highlights the importance of newly formed CD105+ vessels in the bone marrow of MPN patients, and indicates that assessment of CD105‐MVD better reflects angiogenic activity in MPN. In addition, it provides evidence that despite the fact that angiogenesis is generally independent of the JAK2‐V617F status in MPN, new vessel formation might be linked to Jak2 effects in some cases with high JAK2‐V617F mutant allele burden.

Serum Angiopoietin Levels are Different in Acute and Chronic Myeloid Neoplasms: Angiopoietins do not only Regulate Tumor Angiogenesis

“…This finding was in accordance with the literature. A study revealed that there was no association between JAK2-V617F mutational status and MVD and VEGF-expression in BM of MPN patients [19].…”

Numerical impairment of nestin+ bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML

“…3,4 There is increasing evidence that the bone marrow (BM) stem cell niche and endothelial cells are also targets of GvHD. [5][6][7][8][9][10] Moreover, hematopoietic dysfunction, especially thrombocytopenia, is associated with GvHD. 5,8 Marrow failure in such instances is thought to be due to disruption of the donor hematopoiesis by cytokines (especially interferon-γ and tumor necrosis factor-α) released during GvHD.…”

Targeting Angiogenesis in Cancer Treatments: Where do we Stand?

“…Moreover, urine and peripheral blood samples from acute lymphoblastic leukemia patients contained elevated levels of proangiogenic growth factors, namely bFGF and VEGF, which correlated with the increase of bone marrow angiogenesis (56). In support of the role of pro-angiogenic factors in development of blood cancers, significantly increased bone marrow microvascular density and VEGF expression was found in patients with myeloproliferative neoplasms (57). Similarly, increased VEGF production and VEGF receptor expression was detected in three leukemic cell lines (HL-60, HEL, and K562) and primary leukemia samples.…”