LAUSR

The JAK2-V617F mutation is the most common cause of myeloproliferative neoplasms. While experiments have shown that this gain-of-function mutation is associated with myeloid blood cell expansion and increased production of white cells, red cells and platelets, the transcriptional consequences of the JAK2-V617F mutation in different cellular compartments of the bone marrow have not yet been fully elucidated. To study the direct effects of JAK2-V617F on bone marrow cells in myeloproliferative neoplasm patients, we performed joint single-cell RNA sequencing and JAK2 genotyping on CD34+ enriched cells from 8 patients with newly diagnosed essential thrombocythemia or polycythemia vera. We found that the JAK2-V617F mutation increases the expression of interferon-response genes (e.g., HLAs) and the leptin receptor in hematopoietic progenitor cells. Furthermore, we sequenced a population of CD34-bone marrow monocytes and found the JAK2 mutation increased expression of intermediate monocyte genes and the fibrocyte-associated surface protein SLAMF7 in these cells.