Zeitschrift für Leukämie
Offener Zugang
ISSN: 2329-6917
ISSN: 2329-6917
Oliver Bock
The myeloproliferative neoplasms essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are clonal haematological stem cell disorders with different clinical courses and prognosis. The predominant feature in these entities is the overproduction of at least one cellular lineage in the bone marrow. Peripheral blood cells are terminally differentiated and functional but may affect e.g. blood viscosity with a high hematocrit in PV leading to the risk for thrombotic events or bleeding. PMF, preceded by a hypercellular pre-fibrotic stage, has the highest risk to develop manifest bone marrow fibrosis with consecutive bone marrow failure. The risk for a blast crisis and transformation into secondary acute leukemia is also particularly high in PMF and PV but rather uncommon in ET. Even though distinguishable from each other by clinical and histopathological criteria ET, PV and PMF may show overlaps, i.e. in early stages. Moreover, reactive hypercellular states in the bone marrow may mimic a myeloproliferative neoplasm (MPN) making definite molecular markers very useful. ET, PV and PMF currently share a number of molecular defects which are detectable by accurate technologies and, in a diagnostic sense, subsequently allow a clear-cut discriminationfrom reactive states. Some of these molecular defects are frequent in the stage of secondary acute leukemia; others were proposed to be potential predictors for a progression of the disease course. At best, the protagonist of molecular defects in Ph- MPN, the Janus Kinase 2 with its V617F mutation, became a therapeutic target by using small molecule inhibitors. This review focuses on the hitherto discovered molecular defects in ET, PV and PMF in chronic phase and disease progression, highlights some of the current and upcoming therapies and proposes a disease model.