Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition
Acute myeloid leukemia (AML) remains a formidable challenge due to its high relapse rate and limited therapeutic options. This study investigates the role of phosphoinositide-3-kinase-γ (PI3Kγ) in AML and explores the therapeutic potential of the PI3Kγ inhibitor, eganelisib, in preclinical models. U...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2024-12-01
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| Series: | Iraqi Journal of Hematology |
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| Online Access: | https://journals.lww.com/10.4103/ijh.ijh_87_24 |
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| author | Soumyajit Das Mahendra Pratap Singh Nishant Rai Sanjit Sah |
| author_facet | Soumyajit Das Mahendra Pratap Singh Nishant Rai Sanjit Sah |
| author_sort | Soumyajit Das |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) remains a formidable challenge due to its high relapse rate and limited therapeutic options. This study investigates the role of phosphoinositide-3-kinase-γ (PI3Kγ) in AML and explores the therapeutic potential of the PI3Kγ inhibitor, eganelisib, in preclinical models. Using genome-wide CRISPR interference screening, we identified PI3Kγ as a critical survival pathway in certain AML subsets. We demonstrated that inhibition of PI3Kγ with eganelisib disrupts oxidative phosphorylation, thereby impeding AML cell survival and proliferation. Notably, the combination of eganelisib with cytarabine showed enhanced efficacy, suggesting a synergistic interaction that improves treatment outcomes. These findings indicate that PI3Kγ is a viable therapeutic target in AML and that PI3Kγ inhibitors could be pivotal in overcoming treatment resistance and reducing relapse. |
| format | Article |
| id | doaj-art-d0f33b47778449b7b68653b7d26b0a71 |
| institution | Kabale University |
| issn | 2072-8069 2543-2702 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Iraqi Journal of Hematology |
| spelling | doaj-art-d0f33b47778449b7b68653b7d26b0a712025-01-09T13:55:41ZengWolters Kluwer Medknow PublicationsIraqi Journal of Hematology2072-80692543-27022024-12-0113233133310.4103/ijh.ijh_87_24Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibitionSoumyajit DasMahendra Pratap SinghNishant RaiSanjit SahAcute myeloid leukemia (AML) remains a formidable challenge due to its high relapse rate and limited therapeutic options. This study investigates the role of phosphoinositide-3-kinase-γ (PI3Kγ) in AML and explores the therapeutic potential of the PI3Kγ inhibitor, eganelisib, in preclinical models. Using genome-wide CRISPR interference screening, we identified PI3Kγ as a critical survival pathway in certain AML subsets. We demonstrated that inhibition of PI3Kγ with eganelisib disrupts oxidative phosphorylation, thereby impeding AML cell survival and proliferation. Notably, the combination of eganelisib with cytarabine showed enhanced efficacy, suggesting a synergistic interaction that improves treatment outcomes. These findings indicate that PI3Kγ is a viable therapeutic target in AML and that PI3Kγ inhibitors could be pivotal in overcoming treatment resistance and reducing relapse.https://journals.lww.com/10.4103/ijh.ijh_87_24acute myeloid leukemiacrispr screeningeganelisibphosphoinositide-3-kinase-γinhibitiontreatment synergy |
| spellingShingle | Soumyajit Das Mahendra Pratap Singh Nishant Rai Sanjit Sah Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition Iraqi Journal of Hematology acute myeloid leukemia crispr screening eganelisib phosphoinositide-3-kinase-γ inhibition treatment synergy |
| title | Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition |
| title_full | Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition |
| title_fullStr | Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition |
| title_full_unstemmed | Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition |
| title_short | Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition |
| title_sort | expanding the therapeutic horizon in acute myeloid leukemia the role of phosphoinositide 3 kinase γ inhibition |
| topic | acute myeloid leukemia crispr screening eganelisib phosphoinositide-3-kinase-γ inhibition treatment synergy |
| url | https://journals.lww.com/10.4103/ijh.ijh_87_24 |
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