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Diagnosis of Primary Myelofibrosis: World Health Organization (WHO) Criteria

The proposed WHO criteria for the diagnosis of primary myelofibrosis requires all three of the major criteria and at least two of the minor criteria listed below:

Major Criteria
  • Presence of megakaryocyte proliferation and atypia, usually accompanied by either reticulin and/or collagen fibrosis; or, in the absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by increased bone marrow cellularity characterized by granulocytic proliferation and often decreased erythropoiesis (so-called prefibrotic cellular-phase disease)
  • Not meeting criteria for polycythemia vera (p. vera), CML, myelodysplastic syndrome, or other myeloid neoplasm
  • Demonstration of JAK2(V617F) greater than F or other clonal marker; or, in the absence of a clonal marker, no evidence of bone marrow fibrosis caused by an underlying inflammatory disease or another neoplastic disease
    • About 60% of patients with primary myelofibrosis carry a JAK2(V617F) mutation, and about 5% to 10% of the patients have activating mutations in the thrombopoietin receptor gene, MPL
    • Almost 90% of the patients without JAK2(V617F) or MPL carry a somatic mutation of the calreticulin gene, which is associated with a more indolent clinical course than is seen with JAK2(V617F) or MPL mutations
Minor Criteria
  • Leukoerythroblastosis
  • Increased serum level of lactate dehydrogenase
  • Anemia
  • Palpable splenomegaly