Quantitative assessment of innate myeloid cells in myelofibrosis: insights into myeloid and plasmacytoid dendritic cell depletion and disease progression

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis, abnormal hematopoiesis, and extramedullary hematopoiesis. Abnormalities of the tumor microenvironment and immune system may be involved in the MF physiopathology and progression, particularly affecting innate myeloid cells (IMCs) such as myeloid dendritic cells (mDCs), plasmacytoid dendritic cells (pDCs) and monocytes. This study aims to quantitatively assess these cell populations in MF patients and their association with clinical outcomes. A cohort of 21 MF patients from the Universidade Federal de São Paulo was analyzed. Peripheral blood samples were evaluated using flow cytometry to quantify pDCs and monocytic subpopulations, including classical, intermediate, and non-classical monocytes. Comparative analyses were conducted with 12 healthy controls. MF patients exhibited a significant reduction in both the relative and absolute numbers of circulating mDCs and pDCs compared to healthy controls. The pDC reduction was more pronounced in patients with grade 3 fibrosis, anemia and splenomegaly. While total monocyte percentages were slightly lower in MF patient, the distribution of monocytic subpopulations showed no significant differences between groups. Patients with JAK2 mutations demonstrated higher concentrations of intermediate monocytes. The findings reveal a remarkable depletion of pDCs in MF patients, particularly those with advanced clinical manifestations such as anemia and splenomegaly. This study highlights the potential role of dendritic cells as biomarkers for disease severity and progression in MF. Further research is needed to elucidate the functional implications of these cells and their interactions within the MF microenvironment, potentially guiding new diagnostic and therapeutic strategies.