Dietary restriction delays aging. In Nature Medicine, Zhang and colleagues report that fasting alone inhibits the initiation and reverses the progression of B cell and T cell acute lymphoblastic leukemia (ALL), but not that of acute myeloid leukemia (AML), in mouse models. Various regimens of fasting cycles lower the frequency of malignant lymphocytes in the blood and lymphoid organs and enhance survival, if initiated early or late after the transfer of leukemic cells. In ALL cells, but not in non-transformed cells or AML, fasting induces a transcriptional program characterized by activation of the JAK-STAT signaling pathway, lower expression of the oncoprotein n-Myc and the upregulation of cytokine receptors, including the leptin receptor (LEPR). Leptin–LEPR signaling inhibits ALL development through upregulation of the transcription factor Blimp-1, which is important for the terminal differentiation of B cells and T cells. The expression of genes associated with LEPR signaling positively correlates with patient survival in pediatric ALL but not in AML samples.

Nat. Med. (12 December 2016) doi:10.1038/nm.4252