The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis
IntroductionMyeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in C...
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| Format: | Article |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1190305/full |
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| author | Helna Pettersson Jenni Adamsson Peter Johansson Staffan Nilsson Lars Palmqvist Lars Palmqvist Björn Andréasson Julia Asp Julia Asp |
| author_facet | Helna Pettersson Jenni Adamsson Peter Johansson Staffan Nilsson Lars Palmqvist Lars Palmqvist Björn Andréasson Julia Asp Julia Asp |
| author_sort | Helna Pettersson |
| collection | DOAJ |
| description | IntroductionMyeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in CALR and MPL are also frequent. Mutations seen in additional genes are also often the same regardless of subtype of MPN. The aim of this study was to analyze a population based MPN cohort for genetic variants with prognostic value that can guide clinical decisions.MethodsMPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy.ResultsMutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN.DiscussionIn conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered. |
| first_indexed | 2024-03-12T15:14:28Z |
| format | Article |
| id | doaj.art-d60d531c156644268743e2815ef9b0be |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T15:14:28Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-d60d531c156644268743e2815ef9b0be2023-08-11T16:59:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-08-011310.3389/fonc.2023.11903051190305The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosisHelna Pettersson0Jenni Adamsson1Peter Johansson2Staffan Nilsson3Lars Palmqvist4Lars Palmqvist5Björn Andréasson6Julia Asp7Julia Asp8Hematology Section, Department of Medicine, NU Hospital Group, Uddevalla, SwedenDepartment of Laboratory Medicine, University of Gothenburg, Gothenburg, SwedenHematology and Coagulation Section, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Laboratory Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Laboratory Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, SwedenHematology Section, Department of Medicine, NU Hospital Group, Uddevalla, SwedenDepartment of Laboratory Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, SwedenIntroductionMyeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in CALR and MPL are also frequent. Mutations seen in additional genes are also often the same regardless of subtype of MPN. The aim of this study was to analyze a population based MPN cohort for genetic variants with prognostic value that can guide clinical decisions.MethodsMPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy.ResultsMutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN.DiscussionIn conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered.https://www.frontiersin.org/articles/10.3389/fonc.2023.1190305/fullMPNJAK2CALRMPLgermlinemutation |
| spellingShingle | Helna Pettersson Jenni Adamsson Peter Johansson Staffan Nilsson Lars Palmqvist Lars Palmqvist Björn Andréasson Julia Asp Julia Asp The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis Frontiers in Oncology MPN JAK2 CALR MPL germline mutation |
| title | The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis |
| title_full | The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis |
| title_fullStr | The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis |
| title_full_unstemmed | The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis |
| title_short | The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis |
| title_sort | clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis |
| topic | MPN JAK2 CALR MPL germline mutation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1190305/full |
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