Análisis de alteraciones en genes codificantes de proteínas con actividad tirosín quinasa de las familias pdgfr y jak en neoplasias mieloproliferativas crónicas bcr-abl1 negativas

Laburpena

BCR-ABL1 negative chronic myeloproliferative neoplasms (CMPNs) are a heterogeneous group of clonal haematological malignancies. Over the last years, some genetic events in tyrosine kinase (TK) genes have been described as causing events of these diseases. In order to find new somatic aberrations, we have thoroughly analysed by dHPLC and FISH genes from one family of receptor-TKs (family III) and one of cytoplasmatic-TKs (Jak) on samples from 44 BCR-ABL1 negative and V617FJAK2 negative CMPN patients with different phenotypes. At least one member of every family has been reported altered in neoplasia. We have detected several sequence changes, although none of them were frequent events. Remarkably we have identified a new putative activating mutation R340Q in JAK2. Besides, every germline SNP detected did not show a different distribution between patients and controls. On the other hand the hipereosinophilia is a common feature between several hematologic malignancies. This feature had been related to rearrangements involving PDGFRA, PDGFRB, FGFR1 and ETV6. In order to find new fusion genes, we have analysed these genes by FISH and different molecular approaches on samples from 69 hematological neoplasms and eosinophilia. We have found that these genes are not frequently rearranged in these diseases, but we have detected alternative splicing variants from PDGFRA in the majority of samples. However, we could not relate the presence of these transcripts with the development of eosinophilia.