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

Mattia Schino1, Vincenzo Fiorentino2, Elena Rossi3

  • 1Department of Life Sciences and Public Health, Universita Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome. mattia.schino01@icatt.it.

Haematologica
|February 5, 2021
PubMed

Insights

A new bone marrow finding, megakaryocytic activation (M-ACT), helps predict progression in myeloproliferative neoplasms (MPN). This morphological marker aids in personalizing MPN prognosis and differential diagnosis.

Area of Science:

  • Hematology
  • Oncology
  • Pathology

Background:

  • Philadelphia-negative myeloproliferative neoplasms (MPN) traditionally viewed as slow-progressing.
  • Recent evidence indicates rapid evolution in a subset of MPN cases, necessitating personalized prognosis.
  • Current prognostic models for MPN may require refinement to account for diverse disease trajectories.

Purpose of the Study:

  • To identify and validate a novel morphological parameter for predicting MPN progression.
  • To assess the utility of megakaryocytic activation (M-ACT) in differentiating MPN subtypes and predicting outcomes.
  • To investigate the correlation of M-ACT with clinical and molecular features of MPN.

Main Methods:

  • Retrospective analysis of bone marrow biopsies from two MPN cohorts: polycythemia vera (PV) (n=64) and non-PV (essential thrombocythemia, early/prefibrotic primary myelofibrosis [PMF]) (n=222).
  • Definition of M-ACT based on megakaryocytic emperipolesis, MK cluster formation, and collagen fiber arrangement.
  • Correlation analysis of M-ACT with clinical parameters (splenomegaly, WBC, LDH, platelets) and molecular markers (JAK2 V617F, CALR).
  • Progression-free survival analysis comparing patients with and without M-ACT.

Main Results:

  • M-ACT significantly correlated with splenomegaly, white blood cell count, LDH, JAK2 V617F allele burden (in PV), and CALR mutations/platelet count (in non-PV).
  • Patients with M-ACT exhibited significantly worse progression-free survival (PV-to-MF or non-PV-to-overt PMF) in both PV and early/prefibrotic PMF cohorts (P<0.0001).
  • M-ACT was notably absent in essential thrombocythemia patients, suggesting diagnostic utility.

Conclusions:

  • Megakaryocytic activation (M-ACT) is a novel morphological parameter with significant predictive value for MPN progression.
  • M-ACT can aid in the differential diagnosis of MPN, particularly distinguishing aggressive forms.
  • Personalized prognosis in MPN may be enhanced by incorporating M-ACT assessment into routine diagnostics.

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