Suppression of multiple anti‐apoptotic BCL2 family proteins recapitulates the effects of JAK2 inhibitors in JAK2V617F driven myeloproliferative neoplasms

Several lines of research suggest that Bcl‐xL‐mediated anti‐apoptotic effects may contribute to the pathogenesis of myeloproliferative neoplasms driven by JAK2V617F and serve as therapeutic target. Here, we used a knock‐in JAK2V617F mouse model and confirmed that Bcl‐xL was overexpressed in erythroi...

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Veröffentlicht in:	Cancer science 2022-02, Vol.113 (2), p.597-608
Hauptverfasser:	Takei, Hisashi, Coelho‐Silva, Juan Luiz, Tavares Leal, Cristina, Queiroz Arantes Rocha, Adriana, Mantello Bianco, Thiago, Welner, Robert S., Mishima, Yuta, Kobayashi, Ikei S., Mullally, Ann, Lima, Keli, Machado‐Neto, João Agostinho, Kobayashi, Susumu S., Lobo de Figueiredo‐Pontes, Lorena
Format:	Artikel
Sprache:	eng
Schlagworte:	Animal models Animals Antibodies Apoptosis bcl-X Protein - genetics bcl-X Protein - metabolism BCL2 family proteins Blood Bone marrow Cell culture Cell differentiation Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Cytotoxicity Disease Models, Animal Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Enzyme Inhibitors - therapeutic use Erythroid Precursor Cells - pathology Flow cytometry Gene expression Granulocytes Hemopoiesis Humans Indoles - therapeutic use JAK2V617F Janus kinase 2 Janus Kinase 2 - antagonists & inhibitors Janus Kinase 2 - genetics Janus Kinase 2 - metabolism Mice mouse models Mutation Myeloproliferative Disorders - drug therapy Myeloproliferative Disorders - genetics Myeloproliferative Disorders - pathology myeloproliferative neoplasms Neoplasia Nitriles - therapeutic use Original Pathogenesis Peripheral blood Phenotypes Progenitor cells Proteins Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Pyrazoles - therapeutic use Pyrimidines - therapeutic use Pyrroles - therapeutic use Software Spleen Splenomegaly Therapeutic targets Thrombocytopenia Tumor Burden - drug effects Tumors
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