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

Zhigang Lu, Jingjing Xie, Guojin Wu, Jinhui Shen, Robert H Collins, Weina Chen, Xunlei Kang, Min Luo, Yizhou Zou, Jun-Shen Huang, James F Amatruda, Tamra L Slone, Naomi J Winick, Philipp E Scherer, Chengcheng Zhang

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
JournalNature Medicine
DOIs
StateAccepted/In press - Dec 12 2016

Fingerprint

Leptin Receptors
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Tumors
Fasting
Up-Regulation
Pediatrics
T-cells
Neoplasms
Leukemia
Heterografts
Biphenotypic Acute Leukemia
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Genes
Cells
Hematologic Neoplasms
Growth
Acute Myeloid Leukemia
Therapeutics
Maintenance

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation. / Lu, Zhigang; Xie, Jingjing; Wu, Guojin; Shen, Jinhui; Collins, Robert H; Chen, Weina; Kang, Xunlei; Luo, Min; Zou, Yizhou; Huang, Jun-Shen; Amatruda, James F; Slone, Tamra L; Winick, Naomi J; Scherer, Philipp E; Zhang, Chengcheng.

In: Nature Medicine, 12.12.2016.

Research output: Contribution to journalArticle

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AU - Kang, Xunlei

AU - Luo, Min

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AU - Zhang, Chengcheng

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