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Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms

Elisa Rumi and Mario Cazzola

Abstract

Philadelphia-negative classical myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The 2016 revision of the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. Polycythemia vera is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for essential thrombocythemia. Primary myelofibrosis is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of myeloproliferative neoplasms is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Co-mutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of myeloproliferative neoplasms might also allow to accurately evaluate and monitor response to innovative drugs that target the mutant clone.

  • Submitted October 25, 2016.
  • Accepted December 2, 2016.