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Philadelphia-negative chronic myeloproliferative neoplasms (MPN) have been traditionally considered as indistinctly slowly progressing conditions; recent evidence proves that a subset of cases have a rapid evolution, so that MPN prognosis needs to be personalized. We identified a new morphological parameter, defined as megakaryocytic activation (M-ACT) based on the coexistence of megakaryocytic emperipolesis, megakaryocytes (MK) cluster formation and evidence of arrangement of collagen fibers around the perimeter of MK. We retrospectively analyzed the bone marrow biopsy of two MPN cohorts of patients with polycythemia (PV) (n=64) and non-PV patients (including essential thrombocythemia, and early/prefibrotic primary myelofibrosis [PMF]) (n=222). M-ACT showed a significant correlation with splenomegaly, white blood cell count, and lactate dehydrogenase serum levels in both groups, with JAK2 V617F allele burden in PV patients, and with CALR mutations, and platelet count in non-PV patients. Progression-free survival, defined as PV-to-secondary MF progression and non-PV-to-overt PMF, was worse in both PV and early/prefibrotic PMF patients with M-ACT in comparison to those without M-ACT (P&lt;0.0001). Interestingly, M-ACT was not found in the subgroup of essential thrombocythemia patients. In conclusion, M-ACT can be helpful in the differential diagnosis of MPN and can represent a new morphologic parameter with a predictive value for progression of MPN.

Bone marrow megakaryocytic activation predicts fibrotic evolution of Philadelphia-negative myeloproliferative neoplasms