Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation

Developers

Zhigang Lu, Jingjing Xie, Guojin Wu, Philipp E Scherer, Cheng Cheng Zhang, etc.

Description of the technology

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.

The study, performed by the authors of the technology, allowed to reveal that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia, but not acute myeloid leukemia (AML), in mouse models of these tumors. Mechanistically, it was found that attenuated leptin-receptor expression is essential for the development and maintenance of acute lymphoblastic leukemia, and that fasting inhibits acute lymphoblastic leukemia development by upregulation of leptin-receptor and its downstream signaling through the protein PR/SET domain 1. The expression of leptin-receptor signaling-related genes correlated with the prognosis of pediatric patients with pre-B cell acute lymphoblastic leukemia, and fasting effectively inhibited B cell acute lymphoblastic leukemia growth in a human xenograft model.

These 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.

Practical application

Fasting, used in this technology, can serve as an effective therapy of B cell acute lymphoblastic leukemia at both the early and later stages of the disease in patients with de novo and relapsed acute lymphoblastic leukemia.

The technology will be valuable as a new method of acute lymphoblastic leukemia therapy and the study performed in process of its development will serve as a source of useful data for search of new treatment strategies for leukemia.

Laboratories

• Department of Physiology, University of Texas Southwestern Medical Center, Dallas (USA)
• Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (USA)
• BMU-UTSW Joint Taishan Immunology Group, Binzhou Medical University, Yantai, Shandong (China)

Links

Publications

• Lu, Zh. Et al. «Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation." 23 Nature Medicine, (2017): 79–90.
• Kang, X. et al. «The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development." 17 Nat. Cell Biol. (2015): 665–677.
• Zhang, C.C. et al. «Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation." 111 Blood, (2008): 3415–3423.