Increased SLAMF7 monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab.

Maekawa T , Kato S , Kawamura T , Takada K , Sone T , Ogata H , Saito K , Izumi T , Nagao S , Takano K , Okada Y , Tachi N , Teramoto M , Horiuchi T , Hikota-Saga R , Endo-Umeda K , Uno S , Osawa Y , Kobayashi A , Kobayashi S , Sato K , Hashimoto M , Suzu
Monocyte-derived fibrocytes recently garnered attention as 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 healthy controls (HCs). In this study, we evaluated SLAMF7 monocyte percentage in PB of HCs, myeloproliferative neoplasm (MPN) patients without MF, and MPN patients with MF using a cross-sectional approach. We found that MPN patients harboring V617F with MF had a significantly elevated SLAMF7 monocyte percentage, which correlated positively with the V617F allele burden. Additionally, the serum concentration of 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 a useful non-invasive marker 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 not only derived from HCs but also derived from MF patients 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 MF onset in MPN patients harboring V617F, and Elo could be a therapeutic agent for MPN patients harboring V617F with MF.

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