Identification of recurrent genetic aberrations in myeloproliferative neoplasms using an integrated genomics approach.

The recent discoveries of the FIP1L1-PDGFRA fusion gene in chronic eosinophilic leukemia (CEL) and the JAK2 V617F mutation in polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) revolutioned the insights on the molecular oncogenesis of these diseases. Nevertheless, an important fraction of CEL, ET and PMF remains unexplained. In this project, novel genome-wide technologies such as SNP microarrays, massive parallel sequencing and gene expression profiling will be used in a direct and integrated manner on patients with ET and familial or acquired eosinophilia. We expect from this broad approach the discovery of novel critial, not yet described mutations that have e role in the development or progression of these diseases ("driver mutations"). Identification of such novel molecular lesions in HES, CEL and ET can lead to the recognition of new genetic clinicobiological entities. It can improve the current insights on the role of the JAK2 signaling pathway in myeloproliferatieve neoplasms (MPN) as a single event or in cooperation with other genetic aberrations. Furthermore these data might provide novel targets for therapy.

Keywords:Familial eosinophilia, Essential thrombocythemia, FIP1L1-PDGFR, JAK2 V617F, Eosinophilia, Myeloproliferative neoplasms

Disciplines:Morphological sciences, Oncology, Genetics, Systems biology, Molecular and cell biology, Hematology, Laboratory medicine