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

doi:10.1038/nm.4252

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 journal › Article › peer-review

90 Scopus citations

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 language	English (US)
Pages (from-to)	79-90
Number of pages	12
Journal	Nature medicine
Volume	23
Issue number	1
DOIs	https://doi.org/10.1038/nm.4252
State	Published - Jan 1 2017

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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title = "Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation",

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.",

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

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AU - Xie, Jingjing

AU - Wu, Guojin

AU - Shen, Jinhui

AU - Collins, Robert H

AU - Chen, Weina

AU - Kang, Xunlei

AU - Luo, Min

AU - Zou, Yizhou

AU - Huang, Jun-Shen

AU - Amatruda, James F

AU - Slone, Tamra L

AU - Winick, Naomi J

AU - Scherer, Philipp E

AU - Zhang, Chengcheng

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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

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