| Literature DB >> 27941793 |
Zhigang Lu1, Jingjing Xie1,2, Guojin Wu1, Jinhui Shen1, Robert Collins3, Weina Chen4, Xunlei Kang1, Min Luo5, Yizhou Zou6, Lily Jun-Shen Huang7, James F Amatruda8, Tamra Slone8, Naomi Winick8, Philipp E Scherer3,7,9, Cheng Cheng Zhang1,2.
Abstract
New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered for the prevention and treatment of certain solid tumor types. However, whether and how dietary restriction affects hematopoietic malignancies is unknown. Here we report that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AML), in mouse models of these tumors. Mechanistically, we found that attenuated leptin-receptor (LEPR) expression is essential for the development and maintenance of ALL, and that fasting inhibits ALL development by upregulation of LEPR and its downstream signaling through the protein PR/SET domain 1 (PRDM1). The expression of LEPR signaling-related genes correlated with the prognosis of pediatric patients with pre-B-ALL, and fasting effectively inhibited B-ALL growth in a human xenograft model. Our results indicate that the effects of fasting on tumor growth are cancer-type dependent, and they suggest new avenues for the development of treatment strategies for leukemia.Entities:
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Year: 2016 PMID： 27941793 PMCID： PMC6956990 DOI： 10.1038/nm.4252
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440