Role of Vitamins A and D in BCR-ABL Arf−/− Acute Lymphoblastic Leukemia
| Autor: | Monique A. Payton, Kavya Annu, Erin G. Schuetz, Kazuto Yasuda, Brittany Cooper, Julia L. Hurwitz, Cynthia Cline, Samit Ganguly, Laura J. Janke, Kamalika Mukherjee, Sherri L. Surman, Andrea Pesch |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Vitamin Stromal cell Adaptive immunity Fusion Proteins bcr-abl Retinoic acid lcsh:Medicine Apoptosis Bone Marrow Cells T-Lymphocytes Regulatory Article vitamin D deficiency Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases Vitamin D and neurology Animals Medicine Viability assay Vitamin D lcsh:Science Vitamin A Cells Cultured Acute lymphocytic leukaemia Multidisciplinary business.industry lcsh:R Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Chemokine CXCL12 3. Good health Mice Inbred C57BL Leukemia Retinoid X Receptors 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research lcsh:Q Female business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2045-2322 |
| Popis: | The effects of vitamin A and/or vitamin D deficiency were studied in an Arf−/− BCR-ABL acute lymphoblastic leukemia murine model. Vitamin D sufficient mice died earlier (p = 0.003) compared to vitamin D deficient (VDD) mice. Vitamin A deficient (VAD) mice fared worst with more rapid disease progression and decreased survival. Mice deficient for vitamins A and D (VADD) had disease progression similar to VAD mice. Regulatory T cells, previously shown to associate with poor BCR-ABL leukemia control, were present at higher frequencies among CD4+ splenocytes of vitamin A deficient vs. sufficient mice. In vitro studies demonstrated 1,25-dihydroxyvitamin D (1,25(OH)2VD3) increased the number of BCR-ABL ALL cells only when co-cultured with bone marrow stroma. 1,25(OH)2VD3 induced CXCL12 expression in vivo and in vitro in stromal cells and CXCL12 increased stromal migration and the number of BCR-ABL blasts. Vitamin D plus leukemia reprogrammed the marrow increasing production of collagens, potentially trapping ALL blasts. Vitamin A (all trans retinoic acid, ATRA) treated leukemic cells had increased apoptosis, decreased cells in S-phase, and increased cells in G0/G1. ATRA signaled through the retinoid X receptor to decrease BCR-ABL leukemic cell viability. In conclusion, vitamin A and D deficiencies have opposing effects on mouse survival from BCR-ABL ALL. |
| Databáze: | OpenAIRE |
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