”Next generation sequencing – a valuable tool for assessing the impact of additional somatic mutations in young patients with non-BCR-ABL myeloproliferative neoplasms” – [PN-III-P1-1.1-TE-2019-1603], director proiect: Adrian Trifa
| Proposal Registration Code | PN-III-P1-1.1-TE-2019-1603 |
| Project Title | Next generation sequencing – a valuable tool for assessing the impact of additional somatic mutations in young patients with non-BCR-ABL myeloproliferative neoplasms |
| Project Acronym | MYELYOUNG |
| Purpose and project planning | Patients with non-BCR-ABL myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, primary myelofibrosis) harbor specific somatic driver mutations in JAK2, CALR or MPL genes. In recent years, additional mutations in various genes, such as TET2, ASXL1, DNMT3A, SRSF2, U2AF1, have been discovered frequently in these patients. Some of these additional mutations influence the prognosis of these patients. Especially in primary myelofibrosis, additional mutations in several genes have detrimental consequences, decreasing dramatically the overall survival. The role of these additional mutations was analyzed in patients older than 65 years, which represent the greatest proportion of MPN patients. Young patients with MPN (under 40 years old) represent a subgroup very poorly characterized so far. These particular patients seem to have a better prognosis than their older counterparts. The role of additional mutations was not assessed in this subgroup of MPN patients. The project proposes the development of a next generation sequencing (NGS) panel, comprising 13 genes: ASXL1, TET2, U2AF1, SRSF2, EZH2, DNMT3A, IDH1, IDH2, TP53, RUNX1, CBL, SF3B1, SH2B3. Additional mutations will be searched in these genes in 100 young patients (less than 40 years old) and 50 older patients (more than 65 years old), all of them with a definite diagnosis of MPN (harboring one driver mutation in JAK2, CALR or MPL genes). Mutations identified by NGS will be confirmed by Sanger sequencing. We will search for correlations between these additional mutations and various biological and clinical features of the patients included in the study. A comparative analysis of these correlations will be performed between young and older MPN patients. This project will allow us to characterize the landscape of additional mutations, and their consequences, in young patients with non-BCR-ABL MPN. |
| Project Start Date | 15.09.2020 |
| Project End Date | 14.09.2022 |
| Project Duration | 24 months |
| Team: | Trifa Adrian Pavel -> Project leader Banescu Claudia -> Experienced Reearcher Pop Maria Raluca -> post-doctoral researcher Mirea Andreea -> PhD student Badii Medeea -> PhD student Gaal Orsolya Ildiko -> PhD student Tripon Florin -> PhD student Lighezan Diana -> PhD student |
| Results | The design of the NGS panel for the 13 genes to be analysed in the project: ASXL1, TET2, U2AF1, SRSF2, EZH2,DNMT3A, IDH1, IDH2, TP53, RUNX1, CBL, SF3B1, SH2B3, and the implementation of the NGS technique for analysing the 13 genes panel in MPN patients Participation at 1-2 international conferences. – One manuscript describing the NGS technique that we will develop for testing additional mutations. A manuscript describing all the results, prepared for a prestigious journal of hematology. |
| Host institution | George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures |