Fibrogenesis in Primary Myelofibrosis: Diagnostic, Clinical, and Therapeutic Implications

Abstract Primary myelofibrosis is a stem cell-derived clonal malignancy characterized by unchecked proliferation of myeloid cells, resulting in bone marrow fibrosis, osteosclerosis, and pathologic angiogenesis. Bone marrow fibrosis (BMF) plays a central role in the pathophysiology of the disease. This review describes current issues regarding BMF in primary myelofibrosis, including the pathophysiology and impact of abnormal deposition of excess collagen and reticulin fibers in bone marrow spaces, the modified Bauermeister and the European Consensus grading systems of BMF, and the prognostic impact of BMF on the overall outcome of patients with primary myelofibrosis. The impact of novel therapeutic strategies, including JAK-STAT inhibitors and allogeneic stem cell transplant, on BMF is discussed. Implications for Practice: Bone marrow fibrosis (BMF) plays an important role in the pathophysiology and the clinical outcomes of patients with primary myelofibrosis. The severity of BMF correlates with the clinical manifestations of the disease and impacts the survival in patients with myelofibrosis. Treatment with ruxolitinib has been shown to reverse BMF and to continue that trend with ongoing treatment. Further studies to fully understand the mechanisms of fibrosis, to further explore the ability of currently available agents (e.g., JAK-STAT inhibitors) to stabilize and/or reverse fibrosis, and to develop additional fibrosis-targeted therapies are warranted.