التفاصيل البيبلوغرافية
| العنوان: |
In Vivo RNAi Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling |
| المؤلفون: |
Myriam Labelle, Marie McConkey, Richard O. Hynes, Kimberly A. Hartwell, Marcus Järås, Kevin P. Callahan, David E. Root, Glenn S. Cowley, David T. Scadden, Scott A. Armstrong, Lev Silberstein, Gabriela Alexe, Luke Poveromo, Peter Miller, Alexandre Puissant, Muhammad Al-Hajj, Lisa P. Chu, Benjamin L. Ebert, Christopher A. Shelton, John M. Ashton, Fatima Al-Shahrour, Joji Fujisaki, Kimberly Stegmaier, Siddhartha Mukherjee, Rishi V. Puram, Michael G. Kharas, Craig T. Jordan, Sebastian Shterental |
| المصدر: |
Cancer Cell. 24(1):45-58 |
| بيانات النشر: |
Elsevier BV, 2013. |
| سنة النشر: |
2013 |
| مصطلحات موضوعية: |
Cancer Research, Myeloid, Oncogene Proteins, Fusion, Molecular Sequence Data, Syk, Biology, Article, Small hairpin RNA, 03 medical and health sciences, Mice, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Animals, Humans, Progenitor cell, RNA, Small Interfering, beta Catenin, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Base Sequence, Integrin beta3, Myeloid leukemia, Cell Biology, medicine.disease, Hematopoietic Stem Cells, 3. Good health, Mice, Inbred C57BL, Haematopoiesis, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Myeloid-Lymphoid Leukemia Protein, RNA Interference, Signal Transduction |
| الوصف: |
SummaryWe used an in vivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase Syk. In contrast, loss of Itgb3 in normal hematopoietic stem and progenitor cells did not affect engraftment, reconstitution, or differentiation. Finally, using an Itgb3 knockout mouse model, we confirmed that Itgb3 is dispensable for normal hematopoiesis but is required for leukemogenesis. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. |
| تدمد: |
1535-6108 |
| DOI: |
10.1016/j.ccr.2013.05.004 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a6e762545d63fe254cf40e1f269c11dd |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....a6e762545d63fe254cf40e1f269c11dd |
| قاعدة البيانات: |
OpenAIRE |