[The role of driver and subclonal mutations in pathogenesis of primary myelofibrosis].

Primary myelofibrosis (PMF) is a Philadelphia chromosome negative, clonal myeloproliferative neoplasm characterised by a progressive nature. Morphologically, the bone marrow biopsy shows features of abnormal proliferation of terminally differentiated megakaryocytes and subsequent bone marrow fibrosis. The molecular landscape of PMF includes phenotypic driver mutations (JAK2 V617F, CALR and MPL) which represent major diagnostic criteria, and subclonal mutations that also occur in several other myeloid diseases, but have a prognostic value in disease progression of MF. The most important subclonal mutations affect the genes ASXL1, TET2, IDH1/2, EZH2 and TP53. Triple negative genotype and the high molecular risk genotype and CALR-/ASXL1+ are associated with adverse survival with the latest indicating stem cell transplantation independently of the DIPSS-plus score.