Mechanisms by Which Obesity Impacts Survival from Acute Lymphoblastic Leukemia

Abstract

The prevalence of obesity has steadily risen over the past decades, even doubling in more than 70 countries. High levels of body fat (adiposity) and obesity are associated with endocrine and hormonal dysregulation, cardiovascular compromise, hepatic dysfunction, pancreatitis, changes in drug metabolism and clearance, inflammation, and metabolic stress. It is thus unsurprising that obesity can affect the development of and survival from a wide variety of malignancies. This review focuses on acute lymphoblastic leukemia, the most common malignancy in children, to explore the multiple mechanisms connecting acute lymphoblastic leukemia, obesity, and adipocytes, and the implications for leukemia therapy.

Figure 1.

GFP+ 8093 acute lymphoblastic leukemia cells in the perirenal fat pad of a transplanted obese mouse that developed progressive leukemia during vincristine treatment. Lipid is stained with Nile Red, and the image is counterstained with 4', 6-diamidino-2-phenylindole. Image was taken on a Leica DM RXA2 with a x20 objective with x1.6 Optovar magnification (x32 final). Image is representative of fat pads obtained from the other four mice after vincristine treatment. Reprinted with permission from (5).

Figure 2.

Confocal microscopy of adipocytes treated with 60 nM daunorubicin (red) for 4 hours. Photo taken on a LSM 700 confocal system mounted on an AxioObserver.Z1 microscope equipped with a 63/1.4 Plan-APOCHROMAT objective lens and controlled with ZEN 2009 software (Carl Zeiss Microscopy). Reprinted with permission from (60).