A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation
Abstract Although p53 mutations are common in solid tumors, such mutations are found at a lower frequency in hematologic malignancies. In the genetic disorder Fanconi anemia (FA), p53 has been proposed as an important pathophysiological factor for two important hematologic hallmarks of the disease:...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0882-5 |
| _version_ | 1811192552802484224 |
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| author | Wei Du Xiaoli Li Andrew F. Wilson Qishen Pang |
| author_facet | Wei Du Xiaoli Li Andrew F. Wilson Qishen Pang |
| author_sort | Wei Du |
| collection | DOAJ |
| description | Abstract Although p53 mutations are common in solid tumors, such mutations are found at a lower frequency in hematologic malignancies. In the genetic disorder Fanconi anemia (FA), p53 has been proposed as an important pathophysiological factor for two important hematologic hallmarks of the disease: bone marrow failure and leukemogenesis. Here we show that low levels of the p53 protein enhance the capacity of leukemic stem cells from FA patients to repopulate immunodeficient mice. Furthermore, boosting p53 protein levels with the use of the small molecule Nutlin-3 reduced leukemia burden in recipient mice. These results demonstrate that the level of p53 protein plays a crucial role in FA leukemogenesis. |
| first_indexed | 2024-04-11T23:54:32Z |
| format | Article |
| id | doaj.art-d7ebe893fbb74980bf4bb70248c38823 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-11T23:54:32Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-d7ebe893fbb74980bf4bb70248c388232022-12-22T03:56:24ZengBMCStem Cell Research & Therapy1757-65122018-05-01911410.1186/s13287-018-0882-5A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferationWei Du0Xiaoli Li1Andrew F. Wilson2Qishen Pang3Department of Pharmaceutical Sciences, West Virginia University School of PharmacyDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical CenterDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical CenterDivision of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical CenterAbstract Although p53 mutations are common in solid tumors, such mutations are found at a lower frequency in hematologic malignancies. In the genetic disorder Fanconi anemia (FA), p53 has been proposed as an important pathophysiological factor for two important hematologic hallmarks of the disease: bone marrow failure and leukemogenesis. Here we show that low levels of the p53 protein enhance the capacity of leukemic stem cells from FA patients to repopulate immunodeficient mice. Furthermore, boosting p53 protein levels with the use of the small molecule Nutlin-3 reduced leukemia burden in recipient mice. These results demonstrate that the level of p53 protein plays a crucial role in FA leukemogenesis.http://link.springer.com/article/10.1186/s13287-018-0882-5Fanconi anemiaLeukemic stem cellsLeukemogenesisNutlin-3p53 |
| spellingShingle | Wei Du Xiaoli Li Andrew F. Wilson Qishen Pang A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation Stem Cell Research & Therapy Fanconi anemia Leukemic stem cells Leukemogenesis Nutlin-3 p53 |
| title | A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation |
| title_full | A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation |
| title_fullStr | A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation |
| title_full_unstemmed | A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation |
| title_short | A small molecule p53 activator attenuates Fanconi anemia leukemic stem cell proliferation |
| title_sort | small molecule p53 activator attenuates fanconi anemia leukemic stem cell proliferation |
| topic | Fanconi anemia Leukemic stem cells Leukemogenesis Nutlin-3 p53 |
| url | http://link.springer.com/article/10.1186/s13287-018-0882-5 |
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