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Toward prevention of childhood ALL by early-life immune training.

ABSTRACT: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common form of childhood cancer. Chemotherapy is associated with life-long health sequelae and fails in ∼20% of cases. Thus, prevention of leukemia would be preferable to treatment. Childhood leukemia frequently starts before birth, during fetal hematopoiesis. A first genetic hit (eg, the ETV6-RUNX1 gene fusion) leads to the expansion of preleukemic B-cell clones, which are detectable in healthy newborn cord blood (up to 5%). These preleukemic clones give rise to clinically overt leukemia in only ∼0.2% of carriers. Experimental evidence suggests that a major driver of conversion from the preleukemic to the leukemic state is exposure to immune challenges. Novel insights have shed light on immune host responses and how they shape the complex interplay between (1) inherited or acquired genetic predispositions, (2) exposure to infection, and (3) abnormal cytokine release from immunologically untrained cells. Here, we integrate the recently emerging concept of "trained immunity" into existing models of childhood BCP-ALL and suggest future avenues toward leukemia prevention.

SUBMITTER: Hauer J

PROVIDER: S-EPMC8532195 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe obesity rate in preschool children in the United States (US) is 13.9%, while even higher rates are associated with racial and ethnic minorities and children from low-income families. These prevalence patterns underscore the need to identify effective childhood obesity prevention programs.MethodA scoping review was conducted following Arksey and O'Malley's framework to provide an overview of the types, effectiveness and cost-effectiveness of obesity prevention interventions and policies in children up to 6 years old. Inclusion criteria were studies at least 6-months duration; included a weight-based outcome, conducted in the US, English publications from January 2001 to February 2018. Exclusions: studies in overweight/obese children and obesity treatments, no comparator group. Evidence was characterized across the early life course and multiple-levels of influence.ResultsFrom the 2,180 records identified, 34 met the inclusion criteria. Less than half of the interventions initiated during pregnancy, infancy or preschool reported a significant improvement in a weight-based outcome. All interventions included strategies to influence individual- or interpersonal-level health behaviors, yet few removed obstacles in the healthcare system, physical/built environment, or sociocultural environment. The majority (78%) of the interventions occurred during preschool years, with 63% conducted in early childcare education settings serving low-income families. The health impact of the state-wide and national policies on children under age 6 years remains unclear. There was considerable uncertainty around estimates of the health and economic impacts of obesity prevention interventions and policies.ConclusionThere is a need to intensify early childhood obesity preventive efforts during critical periods of health development in the US. Future studies should estimate the feasibility, program effectiveness, and cost of implementing multilevel obesity prevention interventions and policies. Addressing these research gaps will provide stakeholders with the scientific evidence necessary to facilitate funding and policy decisions to decrease the prevalence of early childhood obesity.

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Toward prevention of childhood ALL by early-life immune training.

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