Myelofibrosis
A myeloproliferative neoplasm in which a clonal marrow drives fibroblasts to lay down reticulin and collagen, so the marrow is progressively replaced by fibrosis; blood production shifts to the spleen and liver (extramedullary haematopoiesis), producing massive splenomegaly, a leukoerythroblastic film with tear-drop red cells, and constitutional symptoms.
Definition
Myelofibrosis is a myeloproliferative neoplasm characterised by clonal proliferation of abnormal megakaryocytes and other myeloid cells that drives progressive bone marrow fibrosis, with extramedullary haematopoiesis. It may arise de novo (primary myelofibrosis) or evolve from polycythaemia vera or essential thrombocythaemia (secondary myelofibrosis).
First principles
The clone fibroses its own marrow
The neoplastic clone, usually driven by JAK2, CALR or MPL, includes abnormal megakaryocytes that release excess cytokines and growth factors (such as PDGF and TGF-beta). These stimulate the marrow's non-clonal fibroblasts to deposit reticulin and then collagen. The fibrosis is therefore a reactive consequence of the clone, not a mutation of the fibroblasts themselves, but it progressively crowds out normal haematopoiesis.
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