Molecular pathogenesis of Philadelphia chromosome negative chronic myeloproliferative neoplasms
Clonal hematopoiesis triggered by somatic mutations plays a central role in the pathogenesis of Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPNs). After the discovery of JAK and MPL mutations, continual technological advances have led to the identification of increasing numbers of genetic defects in MPN patients, most of them chromosomal aberrations such as deletions and acquired uniparental disomies. Although efforts to map the genetic lesions to single genes resulted in the discovery of defects in the TET2 and CBL genes, most of the target genes comprised in the chromosomal lesions still remain to be identified. In this review, the different genetic defects found in MPN and their relationships to each other and to disease pathogenesis are critically evaluated. At present, most of the evidence points to a random acquisition of phenotypic and non phenotypic mutations contributing to clonal heterogeneity in MPN. The origin of genetic instability in context of hereditary factors and the common JAK2 haplotype predisposing for the disease are discussed. Furthermore, we address how the choice of therapeutic approaches could be influenced by the genetic complexity.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2011 |
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Erschienen: |
2011 |
Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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Enthalten in: |
Current cancer drug targets - 11(2011), 1 vom: 15. Jan., Seite 20-30 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Jäger, Roland [VerfasserIn] |
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Themen: |
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Anmerkungen: |
Date Completed 18.05.2011 Date Revised 27.10.2019 published: Print Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM203483081 |
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520 | |a Clonal hematopoiesis triggered by somatic mutations plays a central role in the pathogenesis of Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPNs). After the discovery of JAK and MPL mutations, continual technological advances have led to the identification of increasing numbers of genetic defects in MPN patients, most of them chromosomal aberrations such as deletions and acquired uniparental disomies. Although efforts to map the genetic lesions to single genes resulted in the discovery of defects in the TET2 and CBL genes, most of the target genes comprised in the chromosomal lesions still remain to be identified. In this review, the different genetic defects found in MPN and their relationships to each other and to disease pathogenesis are critically evaluated. At present, most of the evidence points to a random acquisition of phenotypic and non phenotypic mutations contributing to clonal heterogeneity in MPN. The origin of genetic instability in context of hereditary factors and the common JAK2 haplotype predisposing for the disease are discussed. Furthermore, we address how the choice of therapeutic approaches could be influenced by the genetic complexity | ||
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