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Mutational Analysis of Driver and Non-driver Mutations of Philadelphia Chromosome-negative Myeloproliferative Neoplasms; Diagnosis and Recent Advances in Treatment

World Journal of Cancer and Oncology Research | Vol 3, Issue 1

Table 3. Simplified 2022 WHO diagnosis criteria forpre-PMF and overt fibrotic PMF; Adapted from: [6, 104].

Early/pre-fibrotic stage PMF (pre-PMF)Overt fibrotic stage PMF
Major Criteria:Major Criteria:
Proliferation of atypical megakaryocytes, accompanied by marrow fibrosis < grade 2*, increased age-adjusted BM cellularity, granulocytic proliferation, but without reticulin fibrosis, and decreased erythropoiesis.Proliferation of atypical megakaryocytes, accompanied by either reticulin and/or collagen fibrosis grade 2 or 3*, osteosclerosis, and extramedullary hematopoiesis.
Criteria for BCR-ABL1, CML, ET, PV, PMF, MDS or other myeloid neoplasms not met.Criteria for BCR-ABL1, CML, ET, PV, PMF, MDS or other myeloid neoplasms not met.
Presence of JAK2, CALR or MPL mutations, or in the absence of these, presence of another clonal marker (e.g., ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1 mutations) or absence of reactive MF.Presence of JAK2, CALR or MPL mutations, or in the absence of these, presence of another clonal marker (e.g., ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1 mutations) or absence of reactive MF.
Minor Criteria:Minor Criteria:
Presence of at least one of the following:Presence of at least one of the following:
AnemiaAnemia
Leukocytosis ≥ 11×109/L.Leukocytosis ≥ 11×109/L.
Palpable splenomegaly.Palpable splenomegaly.
Increased LDH.Increased LDH.
Requirements for diagnosis:Leukoerythroblastosis.
All 3 major criteria + at least 1 minor criterionRequirement for diagnosis:
 All 3 major criteria + at least 1 minor criterion

*PMF shows a higher degree of megakaryocytic atypia than in any other MPN subtype, with distinctive features including small to giant megakaryocytes with cloud-like, hypolobulated, and hyperchromatic nuclei, and the presence of abnormal large dense clusters of >6 megakaryocytes.