Increased SLAMF7 high monocytes in myelofibrosis patients harboring JAK2 V617F provide a therapeutic target of elotuzumab

Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7 monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7 monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored V617F had a significantly elevated SLAMF7 monocyte percentage, which correlated positively with the V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7 monocyte percentage and V617F allele burden. These findings suggest that both SLAMF7 monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the V617F allele burden of SLAMF7 monocytes was significantly higher than that of SLAMF7 monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7 monocytes with higher V617F allele burden was associated with the onset of MF in MPN patients harboring V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor V617F.