دورية أكاديمية
CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia
| العنوان: | CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia |
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| المؤلفون: | Ramakrishnan, Ramprasad, Peña-Martínez, Pablo, Agarwal, Puneet, Rodriguez-Zabala, Maria, Chapellier, Marion, Högberg, Carl, Eriksson, Mia, Yudovich, David, Shah, Mansi, Ehinger, Mats, Nilsson, Björn, Larsson, Jonas, Hagström-Andersson, Anna, Ebert, Benjamin L., Bhatia, Ravi, Järås, Marcus |
| المصدر: | Cell Reports; 31(8), no 107684 (2020) ; ISSN: 2211-1247 |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2020 |
| المجموعة: | Lund University Publications (LUP) |
| مصطلحات موضوعية: | Cell and Molecular Biology, Hematology, acute myeloid leukemia, CRISPR, CXCL12, CXCR4, CXCR4 signaling, differentiation, leukemia stem cell, oxidative stress, ROS, screen |
| الوصف: | Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia cells in vivo without impairing their homing to the bone marrow. In contrast, the CXCR4 ligand CXCL12 is dispensable for leukemia development in recipient mice. Moreover, expression of mutated Cxcr4 variants reveals that CXCR4 signaling is essential for leukemia cells. Notably, loss of CXCR4 signaling in leukemia cells leads to oxidative stress and differentiation in vivo. Taken together, our results identify CXCR4 signaling as essential for AML stem cells by protecting them from differentiation independent of CXCL12 stimulation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://lup.lub.lu.se/record/da408a6e-f1cc-4856-9d03-cf8640695844Test; http://dx.doi.org/10.1016/j.celrep.2020.107684Test; scopus:85085286993; pmid:32460032 |
| DOI: | 10.1016/j.celrep.2020.107684 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2020.107684Test https://lup.lub.lu.se/record/da408a6e-f1cc-4856-9d03-cf8640695844Test |
| رقم الانضمام: | edsbas.1986E9D0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2020.107684 |
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