![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB |
Preview |
PDF (Supplementary Information)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB |
| Item Type: | Article |
|---|---|
| Title: | PLCG1 is required for AML1-ETO leukemia stem cell self-renewal |
| Creators Name: | Schnoeder, T.M., Schwarzer, A., Jayavelu, A.K., Hsu, C.J., Kirkpatrick, J., Döhner, K., Perner, F., Eifert, T., Huber, N., Arreba-Tutusaus, P., Dolnik, A., Assi, S.A., Nafria, M., Jiang, L., Dai, Y.T., Chen, Z., Chen, S.J., Kellaway, S.G., Ptasinska, A., Ng, E.S., Stanley, E.G., Elefanty, A.G., Buschbeck, M., Bierhoff, H., Brodt, S., Matziolis, G., Fischer, K.D., Hochhaus, A., Chen, C.W., Heidenreich, O., Mann, M., Lane, S.W., Bullinger, L., Ori, A., von Eyss, B., Bonifer, C. and Heidel, F. |
| Abstract: | In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a de-regulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells. |
| Keywords: | Acute Myeloid Leukemia, Cell Self Renewal, Core Binding Factor Alpha 2 Subunit, Fusion Oncogene Proteins, Genetic Translocation, Hematopoietic Stem Cells, Leukemic Gene Expression Regulation, Neoplastic Stem Cells, Phospholipase C gamma, Proteome, RUNX1 Translocation Partner 1 Protein, Transcriptome, Animals, Mice |
| Source: | Blood |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Volume: | 139 |
| Number: | 7 |
| Page Range: | 1080-1097 |
| Date: | 17 February 2022 |
| Additional Information: | Copyright © 2022 by The American Society of Hematology |
| Official Publication: | https://doi.org/10.1182/blood.2021012778 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
