title: Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms.
abstract: Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of theWHO Classification of Tumours of Haematopoietic and Lymphoid Tissuesincludes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is,JAK2,CALR, andMPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, andJAK2mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence ofJAK2,CALR, orMPLmutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence ofJAK2,CALR, orMPLmutation. 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 MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, 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 MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone.
authors.affiliation: Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; and.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Elisa
authors.identifier: 0000-0002-7572-9504
authors.initials: E
authors.lastname: Rumi
authors.affiliation: Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; and.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Mario
authors.identifier: 0000-0001-6984-8817
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000367:Age Factors; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D011087:Polycythemia Vera / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2