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Pruritus occurs frequently in patients with polycythemia vera (PV), and the pathophysiology of PV-associated pruritus is unclear. We have previously demonstrated that transgenic mice expressing JAK2V617F displayed clear PV-like phenotypes. In the current study, we found frequent occurrence of pruritus with aged JAK2V617F transgenic mice and further investigated the underlying mechanisms by studying mast cells, key players in allergic reactions and anaphylaxis. Massive accumulations of mast cells were observed in the skin of pruritic JAK2V617F transgenic mice. In vitro culture yielded much higher mast cell counts from the bone marrow, spleen, peripheral blood, and peritoneal cavity of JAK2V617F transgenic mice than from controls. Cultured mast cells from JAK2V617F transgenic mice exhibited enhanced proliferative signals, relative resistance to cell death upon growth factor deprivation, and a growth advantage over control cells under suboptimal growth conditions. However, these mast cells displayed normal morphology and contained normal levels of mast cell proteases before and after degranulation. Finally, the JAK2 inhibitor G6 effectively reduced mast cell numbers and alleviated pruritus in JAK2V617F transgenic mice. Collectively, these data demonstrate that mast cells are involved in PV-associated pruritogenesis and that JAK2 inhibitors are potential antipruritus drugs.

Elevated Levels of Mast Cells Are Involved in Pruritus Associated with Polycythemia Vera in JAK2V617F Transgenic Mice