The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms
<i>CALR</i> mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary myelofibrosis. To date, several <i>CALR</i> mutations were identified, with only frameshift mutation...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3371 |
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| author | Tanja Belčič Mikič Tadej Pajič Samo Zver Matjaž Sever |
| author_facet | Tanja Belčič Mikič Tadej Pajič Samo Zver Matjaž Sever |
| author_sort | Tanja Belčič Mikič |
| collection | DOAJ |
| description | <i>CALR</i> mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary myelofibrosis. To date, several <i>CALR</i> mutations were identified, with only frameshift mutations linked to the diseased phenotype. It is of diagnostic and prognostic importance to properly define the type of <i>CALR</i> mutation and subclassify it according to its structural similarities to the classical mutations, a 52-bp deletion (type 1 mutation) and a 5-bp insertion (type 2 mutation), using a statistical approximation algorithm (AGADIR). Today, the knowledge on the pathogenesis of <i>CALR</i>-positive MPN is expanding and several cellular mechanisms have been recognized that finally cause a clonal hematopoietic expansion. In this review, we discuss the current basis of the cellular effects of <i>CALR</i> mutants and the understanding of its implementation in the current diagnostic laboratorial and medical practice. Different methods of <i>CALR</i> detection are explained and a diagnostic algorithm is shown that aids in the approach to <i>CALR</i>-positive MPN. Finally, contemporary methods joining artificial intelligence in accordance with molecular-genetic biomarkers in the approach to MPN are presented. |
| first_indexed | 2024-03-10T12:55:31Z |
| format | Article |
| id | doaj.art-cb1a9a08fe2f494faff38cf673dbc470 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:55:31Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cb1a9a08fe2f494faff38cf673dbc4702023-11-21T11:59:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227337110.3390/ijms22073371The Contemporary Approach to CALR-Positive Myeloproliferative NeoplasmsTanja Belčič Mikič0Tadej Pajič1Samo Zver2Matjaž Sever3Department of Hematology, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, SloveniaClinical Institute for Genomic Medicine, University Medical Centre Ljubljana, Šlajmerjeva 4, 1000 Ljubljana, SloveniaDepartment of Hematology, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, SloveniaDepartment of Hematology, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia<i>CALR</i> mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary myelofibrosis. To date, several <i>CALR</i> mutations were identified, with only frameshift mutations linked to the diseased phenotype. It is of diagnostic and prognostic importance to properly define the type of <i>CALR</i> mutation and subclassify it according to its structural similarities to the classical mutations, a 52-bp deletion (type 1 mutation) and a 5-bp insertion (type 2 mutation), using a statistical approximation algorithm (AGADIR). Today, the knowledge on the pathogenesis of <i>CALR</i>-positive MPN is expanding and several cellular mechanisms have been recognized that finally cause a clonal hematopoietic expansion. In this review, we discuss the current basis of the cellular effects of <i>CALR</i> mutants and the understanding of its implementation in the current diagnostic laboratorial and medical practice. Different methods of <i>CALR</i> detection are explained and a diagnostic algorithm is shown that aids in the approach to <i>CALR</i>-positive MPN. Finally, contemporary methods joining artificial intelligence in accordance with molecular-genetic biomarkers in the approach to MPN are presented.https://www.mdpi.com/1422-0067/22/7/3371calreticulinchaperonecalciummyeloproliferative neoplasmdiagnosticsthrombocythemia |
| spellingShingle | Tanja Belčič Mikič Tadej Pajič Samo Zver Matjaž Sever The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms International Journal of Molecular Sciences calreticulin chaperone calcium myeloproliferative neoplasm diagnostics thrombocythemia |
| title | The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms |
| title_full | The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms |
| title_fullStr | The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms |
| title_full_unstemmed | The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms |
| title_short | The Contemporary Approach to CALR-Positive Myeloproliferative Neoplasms |
| title_sort | contemporary approach to calr positive myeloproliferative neoplasms |
| topic | calreticulin chaperone calcium myeloproliferative neoplasm diagnostics thrombocythemia |
| url | https://www.mdpi.com/1422-0067/22/7/3371 |
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