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Acute lymphoblastic leukemia, a heterogenous malignancy characterized by uncontrolled proliferation of lymphoid progenitors and generally initiated in utero, is the most common pediatric cancer. Although incidence of ALL has been steadily increasing in recent decades, no clear reason for this trend has been identified. Rising concurrently with ALL incidence, increasing maternal obesity rates may be partially contributing to increasing ALL prevelance. Epidemiological studies, including a recent meta-analysis, have found an association between maternal obesity and leukemogenesis in offspring, although mechanisms underlying this association remain unknown. Therefore, the purpose of this review is to propose possible mechanisms connecting maternal obesity to ALL risk in offspring, including changes to fetal/neonatal epigenetics, altered insulin-like growth factor profiles and insulin resistance, modified adipokine production and secretion, changes to immune cell populations, and impacts on birthweight and childhood obesity/adiposity. We describe how each proposed mechanism is biologically plausible due to their connection with maternal obesity, presence in neonatal and/or fetal tissue, observation in pediatric ALL patients at diagnosis, and association with leukemogenesis, A description of ALL and maternal obesity trends, a summary of epidemiological evidence, a discussion of the pathway from intrauterine environment to subsequent malignancy, and propositions for future directions are also presented. |
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