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Mouse models of myeloproliferative neoplasms for pre-clinical testing of novel therapeutic agents
J. Stetka, RC. Skoda
Language English Country Czech Republic
Document type Journal Article, Review
NLK
Directory of Open Access Journals
from 2001
Free Medical Journals
from 1998
Medline Complete (EBSCOhost)
from 2007-06-01
ROAD: Directory of Open Access Scholarly Resources
from 2001
PubMed
33542546
DOI
10.5507/bp.2021.004
Knihovny.cz E-resources
- MeSH
- Drug Screening Assays, Antitumor * MeSH
- Disease Models, Animal * MeSH
- Myeloproliferative Disorders drug therapy MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Myeloproliferative neoplasms (MPN), are clonal hematopoietic stem cell (HSC) disorders driven by gain-of-function mutations in JAK2 (JAK2-V617F), CALR or MPL genes. MPN treatment options currently mainly consist of cytoreductive therapy with hydroxyurea and JAK2 inhibitors such as ruxolitinib and fedratinib. Pegylated interferon-alpha can induce complete molecular remission (CMR) in some MPN patients when applied at early stages of disease. The ultimate goal of modern MPN treatment is to develop novel therapies that specifically target mutant HSCs in MPN and consistently induce CMR. Basic research has identified a growing number of candidate drugs with promising effects in vitro. A first step on the way to developing these compounds into drugs approved for treatment of MPN patients often consists of examining the effects in vivo using pre-clinical mouse models of MPN. Here we review the current state of MPN mouse models and the experimental setup for their optimal use in drug testing. In addition to novel compounds, combinatorial therapeutic approaches are often considered for the treatment of MPN. Optimized and validated mouse models can provide an efficient way to rapidly assess and select the most promising combinations and thereby contribute to accelerating the development of novel therapies of MPN.
References provided by Crossref.org
Literatura
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- $a Štetka, Ján $7 xx0266843 $u Department of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland $u Department of Biology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
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- $a Myeloproliferative neoplasms (MPN), are clonal hematopoietic stem cell (HSC) disorders driven by gain-of-function mutations in JAK2 (JAK2-V617F), CALR or MPL genes. MPN treatment options currently mainly consist of cytoreductive therapy with hydroxyurea and JAK2 inhibitors such as ruxolitinib and fedratinib. Pegylated interferon-alpha can induce complete molecular remission (CMR) in some MPN patients when applied at early stages of disease. The ultimate goal of modern MPN treatment is to develop novel therapies that specifically target mutant HSCs in MPN and consistently induce CMR. Basic research has identified a growing number of candidate drugs with promising effects in vitro. A first step on the way to developing these compounds into drugs approved for treatment of MPN patients often consists of examining the effects in vivo using pre-clinical mouse models of MPN. Here we review the current state of MPN mouse models and the experimental setup for their optimal use in drug testing. In addition to novel compounds, combinatorial therapeutic approaches are often considered for the treatment of MPN. Optimized and validated mouse models can provide an efficient way to rapidly assess and select the most promising combinations and thereby contribute to accelerating the development of novel therapies of MPN.
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