Pathogenesis of myeloproliferative neoplasms
| Autor: | Jean Grisouard, Adrian Duek, Radek C. Skoda |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Disease Gene mutation Biology medicine.disease_cause Pathogenesis medicine Genetics Animals Humans Epigenetics Transcription factor Molecular Biology Regulation of gene expression Mutation Myeloproliferative Disorders food and beverages Cell Biology Hematology Phenotype Neoplasm Proteins 3. Good health Gene Expression Regulation Neoplastic Hematologic Neoplasms Signal Transduction |
| Zdroj: | Experimental hematology |
| ISSN: | 0301-472X |
| DOI: | 10.1016/j.exphem.2015.06.007 |
| Popis: | Major progress has been recently made in understanding the molecular pathogenesis of myeloproliferative neoplasms (MPN). Mutations in one of four genes-JAK2, MPL, CALR, and CSF3R-can be found in the vast majority of patients with MPN and represent driver mutations that can induce the MPN phenotype. Hyperactive JAK/STAT signaling appears to be the common denominator of MPN, even in patients with CALR mutations and the so-called "triple-negative" MPN, where the driver gene mutation is still unknown. Mutations in epigenetic regulators, transcription factors, and signaling components modify the course of the disease and can contribute to disease initiation and/or progression. The central role of JAK2 in MPN allowed development of small molecular inhibitors that are in clinical use and are active in almost all patients with MPN. Advances in understanding the mechanism of JAK2 activation open new perspectives of developing the next generation of inhibitors that will be selective for the mutated forms of JAK2. |
| Databáze: | OpenAIRE |
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