Mesenchymal stromal cells secretory pattern contributes to oncoinflammatory bone marrow microenvironment in polycythemia vera.

INTRODUCTION: Polycythemia vera is a myeloproliferative neoplasm marked by an increased proliferation of erythroid mature and precursors cells in bone marrow and peripheral blood. The pathophysiology is linked to the presence of the JAK2 driver mutation, epigenetic deregulation, and alterations in the bone marrow hematopoietic niche. Multipotent mesenchymal stromal cells (MSC) in the bone marrow, which are crucial for maintenance and development of hematopoietic stem cells, play a role in the communication between neoplastic cells and resident bone marrow cells by releasing various mediators that either suppress or promote tumor progression. These mediators include several essential immunomodulatory molecules, pro-angiogenic and growth factors. We hypothesized that MSC from polycythemia vera patients (Patient Group) would exhibit distinct properties compared to those from healthy donors (Control Group), thereby influencing the hematopoietic niche and contributing to disease pathogenesis. METHODS: This study characterized MSC from patients, focusing on their secretory, proteomic, and phenotypic properties. RESULTS: MSC from the Patient and Control Groups had similar immunophenotypes and multipotentiality. However, MSC from the Patient Group exhibited reduced immunomodulatory properties, and released distinct soluble immune and angiogenic mediators when compared with the Control Group. Global proteomic analysis revealed that MSC from patients presented upregulated expressions of FAM175B, VP526A, CTTN, MAP4, BAX, and TPD52L2 but a downregulated TNC expression. These results indicate that MSC contribute to the inflammation pattern in the hematopoietic niche. The secretory and proteomic profile of MSC from patients, indicate that these cells may influence immune cell function, induce neoangiogenesis, and alter cell-to-cell interactions within the bone marrow, thereby fostering a pro-tumor microenvironment and favoring disease pathogenesis. CONCLUSION: These findings highlight the potential of targeting MSC-mediated pathways as a therapeutic strategy in polycythemia vera.