Experimental Modeling of Myeloproliferative Neoplasms
| Autor: | Josef T. Prchal, Olga Babosova, Lucie Lanikova |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MPL mpl Review medicine.disease_cause Germline MPN (myeloproliferative neoplasms) 0302 clinical medicine Genome editing calr Neoplasms CRISPR Induced pluripotent stem cell Zebrafish Polycythemia Vera Genetics (clinical) Mutation biology food and beverages Phenotype JAK2 030220 oncology & carcinogenesis Receptors Thrombopoietin Signal Transduction Thrombocythemia Essential mice lcsh:QH426-470 Induced Pluripotent Stem Cells iPSCs Computational biology 03 medical and health sciences Germline mutation Genetics medicine Animals Humans CALR thrombosis jak2 Myeloproliferative Disorders Cas9 Janus Kinase 2 biology.organism_classification lcsh:Genetics Disease Models Animal 030104 developmental biology Primary Myelofibrosis Calreticulin |
| Zdroj: | Genes Genes, Vol 10, Iss 10, p 813 (2019) |
| ISSN: | 2073-4425 |
| Popis: | Myeloproliferative neoplasms (MPN) are genetically very complex and heterogeneous diseases in which the acquisition of a somatic driver mutation triggers three main myeloid cytokine receptors, and phenotypically expresses as polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The course of the diseases may be influenced by germline predispositions, modifying mutations, their order of acquisition and environmental factors such as aging and inflammation. Deciphering these contributory elements, their mutual interrelationships, and their contribution to MPN pathogenesis brings important insights into the diseases. Animal models (mainly mouse and zebrafish) have already significantly contributed to understanding the role of several acquired and germline mutations in MPN oncogenic signaling. Novel technologies such as induced pluripotent stem cells (iPSCs) and precise genome editing (using CRISPR/Cas9) contribute to the emerging understanding of MPN pathogenesis and clonal architecture, and form a convenient platform for evaluating drug efficacy. In this overview, the genetic landscape of MPN is briefly described, with an attempt to cover the main discoveries of the last 15 years. Mouse and zebrafish models of the driver mutations are discussed and followed by a review of recent progress in modeling MPN with patient-derived iPSCs and CRISPR/Cas9 gene editing. |
| Databáze: | OpenAIRE |
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