Is There a Causal Relationship between Childhood Obesity and Acute Lymphoblastic Leukemia? A Review

SIMPLE SUMMARY: The childhood obesity epidemic is impacting tens of millions of children globally. While obesity causes several cancers in adults, its potential role in causing pediatric cancers remains unclear. In this review, we assess the potential contribution of obesity to the development of acute lymphoblastic leukemia (ALL), the most common pediatric cancer. We review the possible mechanisms by which the adipose tissue attracts and protects leukemia cells and how it interferes with the actions of chemotherapies used in ALL treatment. We also examine adipose tissue-secreted molecules and fuels that may support leukemia development. While there are no current definite causal links between obesity and ALL, there are plausible mechanisms that need further investigation to explore the impact of obesity on causing ALL and on impacting treatment outcomes. ABSTRACT: Childhood obesity is a growing epidemic with numerous global health implications. Over the past few years, novel insights have emerged about the contribution of adult obesity to cancer risk, but the evidence base is far more limited in children. While pediatric patients with acute lymphoblastic leukemia (ALL) are at risk of obesity, it is unclear if there are potential causal mechanisms by which obesity leads to ALL development. This review explores the endocrine, metabolic and immune dysregulation triggered by obesity and its potential role in pediatric ALL’s genesis. We describe possible mechanisms, including adipose tissue attraction and protection of lymphoblasts, and their impact on ALL chemotherapies’ pharmacokinetics. We also explore the potential contribution of cytokines, growth factors, natural killer cells and adipose stem cells to ALL initiation and propagation. While there are no current definite causal links between obesity and ALL, critical questions persist as to whether the adipose tissue microenvironment and endocrine actions can play a causal role in childhood ALL, and there is a need for more research to address these questions.