AI Article Synopsis
- Researchers conducted a detailed analysis to find new drugs for treating acute myeloid leukemia (AML) caused by fusion genes, specifically focusing on AML1-ETO (AE) driven AML.
- They discovered that the fusion protein AE disrupts phospholipase C (PLC) signaling, with PLCgamma 1 (PLCG1) being a vital target that affects the leukemia's self-renewal and growth.
- Inactivating PLCG1 in both mouse and human models led to reduced leukemia maintenance, while not affecting normal blood cell functions, suggesting that targeting the PLCG1 pathway could be a promising therapeutic strategy for AML1-ETO+ leukemia.
Article 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 deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that 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+ leukemic stem cells.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854675 | PMC |
| http://dx.doi.org/10.1182/blood.2021012778 | DOI Listing |
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