Angiogenesis in JAK2 V617F positive myeloproliferative neoplasms and ruxolitinib decrease VEGF, HIF-1 enesis in JAK2 V617F positive cells

Abstract

Angiogenesis and JAK2 V617F mutation are common in BCR-ABL1 negative myeloproliferative neoplasms (MPNs). Ruxolitinib, a JAK inhibitor, is an effective treatment for some MPNs. However, the relationship between angiogenesis and JAK2 V617F and the effects of ruxolitinib on angiogenesis are still unknown. Here, we observed the correlation of JAK2 V617F mutation burden with VEGF, HIF-1a and microvascular density (MVD) in MPNs. We investigate the effect of ruxolitinib on the expression of VEGF and HIF-1α in JAK2 V617F positive cells. We found the expression levels of p-JAK2, VEGF, HIF-1a and MVD in the newly diagnosed MPNs were significantly increased and were related to the JAK2 V617F burden. Ruxolitinib can inhibit p-JAK2, VEGF, HIF-1a expression and suppress blood vessels’ formation in chick embryo choriallantoic membrane. Our findings indicated that angiogenesis is related to JAK2 V617F burden and ruxolitinib could decrease VEGF and HIF-1a expression in JAK2 V617F positive cells.

Keywords:

• Myeloproliterative neoplasms
• ruxolitinib
• JAK2 V617F mutation
• VEGF
• HIF-1α
• angiogenesis

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1324155.

Additional information

Funding

This work was supported by Hebei Province Science and Technology Support Program, China, under Grant [No. 162777120D].