The Current Molecular Site of the Myeloproliferative Neoplasms - TET-á-tête with the Jackpot but no LNK so far to Resolve Complexity
Institute of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Germany
- *Corresponding Author:
- Oliver Bock
Department of Psychiatry
Social Psychiatry and Psychotherapy
Hannover Medical School
30625 Hannover, Germany
E-mail: [email protected]
Received date February 20, 2013; Accepted date April 05, 2013; Published date April 08, 2013
Citation: Bock O (2013) The Current Molecular Site of the Myeloproliferative Neoplasms - TET-á-tête with the Jackpot but no LNK so far to Resolve Complexity. J Leuk (Los Angel) 1:108. doi: 10.4172/2329-6917.1000108
Copyright: © 2013 Bock O. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 discrimination from 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.