Mouse models of mantle cell lymphoma, complex changes in gene expression and phenotype of engrafted MCL cells: implications for preclinical research
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24862967
DOI
10.1038/labinvest.2014.61
PII: S0023-6837(22)00822-4
Knihovny.cz E-zdroje
- MeSH
- imunofenotypizace MeSH
- imunohistochemie MeSH
- játra metabolismus MeSH
- Kaplanův-Meierův odhad MeSH
- kostní dřeň metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom z plášťových buněk farmakoterapie genetika metabolismus MeSH
- modely nemocí na zvířatech * MeSH
- mozek metabolismus MeSH
- myši inbrední NOD MeSH
- myši knockoutované MeSH
- myši SCID MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádorové buňky kultivované MeSH
- receptory interleukinů - společná gama-podjednotka nedostatek genetika MeSH
- regulace genové exprese u nádorů * MeSH
- senioři MeSH
- slezina metabolismus MeSH
- transkriptom genetika MeSH
- transplantace heterologní MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Il2rg protein, mouse MeSH Prohlížeč
- receptory interleukinů - společná gama-podjednotka MeSH
Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin lymphoma (NHL) associated with poor prognosis. Animal models of MCL are scarce. We established and characterized various in vivo models of metastatic human MCL by tail vein injection of either primary cells isolated from patients with MCL or established MCL cell lines (Jeko-1, Mino, Rec-1, Hbl-2, and Granta-519) into immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. MCL infiltration was assessed with immunohistochemistry (tissues) and flow cytometry (peripheral blood). Engraftment of primary MCL cells was observed in 7 out of 12 patient samples. The pattern of engraftment of primary MCL cells varied from isolated involvement of the spleen to multiorgan infiltration. On the other hand, tumor engraftment was achieved in all five MCL cell lines used and lymphoma involvement of murine bone marrow, spleen, liver, and brain was observed. Overall survival of xenografted mice ranged from 22 ± 1 to 54 ± 3 days depending on the cell line used. Subsequently, we compared the gene expression profile (GEP) and phenotype of the engrafted MCL cells compared with the original in vitro growing cell lines (controls). We demonstrated that engrafted MCL cells displayed complex changes of GEP, protein expression, and sensitivity to cytotoxic agents when compared with controls. We further demonstrated that our MCL mouse models could be used to test the therapeutic activity of systemic chemotherapy, monoclonal antibodies, or angiogenesis inhibitors. The characterization of MCL murine models is likely to aid in improving our knowledge in the disease biology and to assist scientists in the preclinical and clinical development of novel agents in relapsed/refractory MCL patients.
1st Faculty of Medicine Institute of Pathology Charles University Prague
Institute of Hematology and Blood Transfusion Prague Czech Republic
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