Onkologie. 2012:6(3):146-151

Molecular Genetics in Diagnosis and Prognosis of Philadelphia Chromosome Negative Myeloproliferative Neoplasms. Molecular genetics in MPNs

Alessandro M.Vannucchi, Paola Guglielmelli

Section of Hematology, Department of Critical Care, University of Florence, Italy

Chronic myeloproliferative neoplasms (MPNs) represent a heterogeneous group of myeloid neoplasia whose molecular asset is marked

by the presence of a JAK2V617F mutation. Following this seminal discovery, several other mutations have been identified highlighting an

unexpected molecular complexity. Deregulation of the JAK/STAT pathway is a central feature of MPNs and, although it has raised much

interest for the possibility of targeted therapy with JAK2 inhibitors, it has been realized that JAK2 mutations are secondary mutational

events in most, if not all, cases. Another recurrent theme is the involvement of genes intervening in the epigenetic control of gene expression

and, more recently, in RNA splicing. Most of these mutations are shared by patients with myelodysplastic syndromes as well.

Studies focusing on the complex clonal hierarchy of MPNs suggest a condition of genetic instability, that could be either acquired or

inherited. At this regard, the discovery of a specific germline haplotype in JAK2 provided an explanation for the phenomenon of familial

clustering of MPNs, although other still unknown haplotypes are likely involved. The aim of this review is to summarize current knowledge of molecular abnormalities of MPNs and discuss their role for diagnosis and prognosis.

Klíčová slova: myeloproliferative neoplasms, mutations, JAK2, prognosis.

Zveřejněno: 31. červenec 2012  Zobrazit citaci