Pathogenesis

• Clonal neoplastic proliferation arising from early haematopoietic stem cell.

• May evolve from PV (~9% of cases evolve into MF) or ET (~2% of cases evolve to MF); minority may follow previous chemotherapy or

256 radiotherapy.

• Haemopoietic cells clonal, fibroblasts not clonal.

• Fibrosis is a cytokine-mediated reactive process (TGF-|3, PDGF, IL-1, EGF, calmodulin and |3FGF); can develop in response to chronic myeloproliferative disorders, myelodysplasia and secondary carcinoma.

• Exaggeration of normal BM reticulin pattern progresses to intense collagen fibrosis which disrupts and finally obliterates normal marrow architecture; ultimately osteosclerosis may develop.

• High levels of immature progenitors appear in PB.

• Extramedullary haemopoiesis develops in spleen and/or liver-occasion-ally other sites, e.g. lymph nodes, skin and serosal surfaces.

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