title: Diet-induced obesity accelerates acute lymphoblastic leukemia progression in two murine models.
abstract: Obesity is associated with an increased incidence of many cancers, including leukemia, although it is unknown whether leukemia incidence is increased directly by obesity or rather by associated genetic, lifestyle, health, or socioeconomic factors. We developed animal models of obesity and leukemia to test whether obesity could directly accelerate acute lymphoblastic leukemia (ALL) using BCR/ABL transgenic and AKR/J mice weaned onto a high-fat diet. Mice were observed until development of progressive ALL. Although obese and control BCR/ABL mice had similar median survival, older obese mice had accelerated ALL onset, implying a time-dependent effect of obesity on ALL. Obese AKR mice developed ALL significantly earlier than controls. The effect of obesity was not explained by WBC count, thymus/spleen weight, or ALL phenotype. However, obese AKR mice had higher leptin, insulin, and interleukin-6 levels than controls, and these obesity-related hormones all have potential roles in leukemia pathogenesis. In conclusion, obesity directly accelerates presentation of ALL, likely by increasing the risk of an early event in leukemogenesis. This is the first study to show that obesity can directly accelerate the progression of ALL. Thus, the observed associations between obesity and leukemia incidence are likely to be directly related to biological effects of obesity.
authors.affiliation: Division of Endocrinology, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Yun
authors.forename: James W
authors.initials: JW
authors.lastname: Behan
authors.forename: Nora
authors.initials: N
authors.lastname: Heisterkamp
authors.forename: Anna
authors.initials: A
authors.lastname: Butturini
authors.forename: Lars
authors.initials: L
authors.lastname: Klemm
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ji
authors.forename: John
authors.initials: J
authors.lastname: Groffen
authors.forename: Markus
authors.initials: M
authors.lastname: Müschen
authors.forename: Steven D
authors.initials: SD
authors.lastname: Mittelman
mesh_terms: D052242:Adiponectin / Q000097:blood; D017668:Age of Onset; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D018450:Disease Progression; D016313:Genes, abl / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D051379:Mice; D008806:Mice, Inbred AKR; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000150:complications*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000235:genetics
chemical_list: D052242:Adiponectin; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin
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