Diagnostic and treatment guidelines for the chronic myeloproliferative neoplasms: current challenges

Abstract

ISSN 2045-1393 Int. J. Hematol. Oncol. (2015) 4(1), 5–8 The chronic myeloproliferative neoplasms (MPN), polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) are a unique group of hematopoietic stem cell disorders, characterized by the increased production of morphologically normal red cells, white cells and platelets alone or in combination and a tendency to develop myelofibrosis, extramedullary hematopoiesis with bone marrow failure or leukemic transformation, albeit at varying frequencies. These shared clinical features not only result in phenotypic mimicry among these three disorders but also between them, their companion myeloid neoplasms (MN) and certain benign disorders of hematopoiesis as well. In this regard, although they are clonal stem cell disorders, the chronic MPN differ from their companion MN because with supportive therapy alone, survival in PV, ET and PMF is usually measured not in years but decades. This makes diagnostic accuracy essential. However, until the 2005 discovery of a mutation (V617F) in JAK2 [1], a tyrosine kinase essential for hematopoietic progenitor cell proliferation and differentiation, the diagnosis of a specific MPN was largely based on clinical phenotype and, in particular exclusion of absolute erythrocytosis [2], the hall mark of PV, the most common MPN and the one in which the risk of thrombosis or hemorrhage is greatest. The development of a clinical assay for JAK2 V617F and subsequently, for mutations in JAK2 exon 12, redefined the MPN on a molecular basis with approximately 95% of PV patients expressing JAK2 V617F and 3% expressing JAK2 exon 12 mutations. By contrast, only 50–60% of ET and PMF patients expressed JAK2 V617F; the discovery of MPL mutations primarily in 4% of ET and 8% of PMF patients still left approximately 30–40% of MPN patients, including some with PV, without an identified molecular basis for their disease. In 2007, taking advantage of these molecular findings, the WHO proposed new diagnostic criteria for the MPN, relying on the use of molecular assays for JAK2 and MPL mutations together with stipulated values for the hemoglobin or hematocrit value, the use of the serum erythropoietin (EPO) level, endogenous erythroid colony formation, bone marrow histology, cytogenetics and flow cytometry