Genomics of racial and ethnic disparities in childhood acute lymphoblastic leukemia

Abstract

Although the cure rates of childhood acute lymphoblastic leukemia (ALL) have improved dramatically in the past 40 years, not all children have benefited equally from this impressive progress. Racial and ethnic disparities in the incidence and treatment outcome of childhood ALL persist, with Hispanic children having an elevated risk of developing ALL and one of the lowest survival rates after ALL therapy. A critical barrier to progress is the lack of an understanding of the causes of ALL disparities, particularly racial and ethnic differences in ALL biology. In this review, the authors summarize the current knowledge on population variation in childhood ALL incidence and treatment outcome, discuss the contributing genetic and nongenetic variables, and highlight possible therapeutic interventions to mitigate disparities in ALL.

Keywords: childhood; disparity; ethnicity; genomics; leukemia; race.

Figure 1. Genetic and non-genetic factors influencing racial and ethnic disparities in childhood ALL

Figure 2. Genetic ancestry and risk of relapse in childhood ALL

(a) Genetic ancestral composition of 2,534 children with ALL. Each patient's ancestry is shown as a column and the color represents the proportion of ancestry estimated for that patient (European, red; African, gray; Asian, green; Native American, blue). Genetic ancestry was estimated using STRUCTURE. Patients were clustered using the Ward clustering method based on dissimilarity in genetic ancestry measured by 1-minus pair-wise correlation. (b–e) Higher levels of Native American (NA) ancestry were linked to increased risk of relapse in all patients (b) and within the self-reported European American (c) and for those who did not receive delayed intensification (d) but not within those who did receive delayed intensification in the COG P9904/9905 trial (e). Although cumulative incidence of relapse is plotted separately for patients with <10% (red) versus ≥10% (blue) Native American ancestry, we estimated all P values using a Fine and Gray's cumulative incidence hazard regression model treating Native American ancestry as a continuous. (Reproduced with permission from Yang JJ, Cheng C, Devidas M et al., Nature Genetics, 43, 240, 2011)