Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells
Summary: Leukemic-stem-cell-specific targeting may improve the survival of patients with acute myeloid leukemia (AML) by avoiding the ablative effects of standard regimens on normal hematopoiesis. Herein, we perform an unbiased screening of compounds targeting cell surface proteins and identify clin...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472300116X |
| _version_ | 1797903374564196352 |
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| author | Chen Wang Ravi Nistala Min Cao Yi Pan Madelaine Behrens Donald Doll Richard D. Hammer Puja Nistala Hui-Ming Chang Edward T.H. Yeh XunLei Kang |
| author_facet | Chen Wang Ravi Nistala Min Cao Yi Pan Madelaine Behrens Donald Doll Richard D. Hammer Puja Nistala Hui-Ming Chang Edward T.H. Yeh XunLei Kang |
| author_sort | Chen Wang |
| collection | DOAJ |
| description | Summary: Leukemic-stem-cell-specific targeting may improve the survival of patients with acute myeloid leukemia (AML) by avoiding the ablative effects of standard regimens on normal hematopoiesis. Herein, we perform an unbiased screening of compounds targeting cell surface proteins and identify clinically used DPP4 inhibitors as strong suppressors of AML development in both murine AML models and primary human AML cells xenograft model. We find in retrovirus-induced AML mouse models that DPP4-deficient AML cell-transplanted mice exhibit delay and reversal of AML development, whereas deletion of DPP4 has no significant effect on normal hematopoiesis. DPP4 activates and sustains survival of AML stem cells that are critical for AML development in both human and animal models via binding with Src kinase and activation of nuclear factor κB (NF-κB) signaling. Thus, inhibition of DPP4 is a potential therapeutic strategy against AML development through suppression of survival and stemness of AML cells. |
| first_indexed | 2024-04-10T09:31:53Z |
| format | Article |
| id | doaj.art-4fd2c19656ae473ea08c0f7aeb939853 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T09:31:53Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4fd2c19656ae473ea08c0f7aeb9398532023-02-19T04:25:34ZengElsevierCell Reports2211-12472023-02-01422112105Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cellsChen Wang0Ravi Nistala1Min Cao2Yi Pan3Madelaine Behrens4Donald Doll5Richard D. Hammer6Puja Nistala7Hui-Ming Chang8Edward T.H. Yeh9XunLei Kang10Center for Precision Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USACenter for Precision Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA; Division of Nephrology, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USACenter for Precision Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USACenter for Precision Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USACenter for Precision Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USADivision of Hematology and Oncology, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USADepartment of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USADivision of Hematology and Oncology, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USADepartment of Pharmacology and Toxicology, The University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Internal Medicine, The University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Internal Medicine, The University of Arkansas for Medical Sciences, Little Rock, AR 72205, USACenter for Precision Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA; Division of Hematology and Oncology, Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA; Corresponding authorSummary: Leukemic-stem-cell-specific targeting may improve the survival of patients with acute myeloid leukemia (AML) by avoiding the ablative effects of standard regimens on normal hematopoiesis. Herein, we perform an unbiased screening of compounds targeting cell surface proteins and identify clinically used DPP4 inhibitors as strong suppressors of AML development in both murine AML models and primary human AML cells xenograft model. We find in retrovirus-induced AML mouse models that DPP4-deficient AML cell-transplanted mice exhibit delay and reversal of AML development, whereas deletion of DPP4 has no significant effect on normal hematopoiesis. DPP4 activates and sustains survival of AML stem cells that are critical for AML development in both human and animal models via binding with Src kinase and activation of nuclear factor κB (NF-κB) signaling. Thus, inhibition of DPP4 is a potential therapeutic strategy against AML development through suppression of survival and stemness of AML cells.http://www.sciencedirect.com/science/article/pii/S221112472300116XCP: Cancer |
| spellingShingle | Chen Wang Ravi Nistala Min Cao Yi Pan Madelaine Behrens Donald Doll Richard D. Hammer Puja Nistala Hui-Ming Chang Edward T.H. Yeh XunLei Kang Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells Cell Reports CP: Cancer |
| title | Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells |
| title_full | Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells |
| title_fullStr | Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells |
| title_full_unstemmed | Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells |
| title_short | Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells |
| title_sort | dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S221112472300116X |
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