SLAMF7 as a potential therapeutic target in MF. (A) In the peripheral blood of MF patients, there is an increase in the percentage of SLAMF7^highCD16^– monocytes and this positively correlates with the JAK2V617F allele burden. Clonal involved, monocyte-derived fibrocytes drive BM fibrosis through cytokine production and other unknown mechanisms. They specifically promote deposition of reticulin fibrosis in the BM and may contribute to splenomegaly. (B) The authors showed that monocytes from MF patients treated with the anti-SLAMF7 antibody elotuzumab result in reduction of fibrocyte differentiation. Treatment of a romiplostim-induced myelofibrotic mouse model with elotuzumab resulted in decreased BM fibrosis and reduction in spleen size. This serves as preclinical evidence that elotuzumab may modulate the BM microenvironment in MF patients and provide a more hospitable environment for normal hematopoiesis. (C) Elotuzumab targets the BM microenvironment through inhibiting differentiation of SLAMF7^highCD16^– to neoplastic fibrocytes; however, it is unlikely that this agent has any effect on the MPN hematopoietic stem cells. A combination therapy approach targeting the MPN hematopoietic stem cells and restoring the BM microenvironment would likely be the most effective strategy to achieve disease course modification.