Racial differences in clinical and cytogenetic features of pediatric acute myeloid leukemia

Introduction: Racial disparities in pediatric acute myeloid leukemia (AML) outcomes are well documented, yet the biological basis for these differences remains poorly understood. Despite the availability of molecular technologies, their use in characterizing ancestry-associated disease variation has been limited. In this study, we aimed to profile race-associated clinical and molecular features in pediatric patients with AML. Methods: We utilized the pediatric TARGET AML 2018 cohort, which included samples from 899 patients with clinical, genomic, and transcriptomic data. All data were retrieved and analyzed through the cBioportal data repository. Analyses were limited to race groups with at least 20 cases (White, Black/African American, and Asian). X2 and Kruskal-Wallis tests were used to compare categorical and continuous features, respectively. Results: Of 899 patients, 836 patients had data reported on race, of which the majority were White (n = 644, 77.03%), followed by Black/African American (n = 102, 12.20%), Asian (n = 43, 5.14%), and other racial minorities (n=47, 5.62%). Age at diagnosis was comparable across race groups (median 11-12), and there was a trend for increased female percentage in Asian patients (61.22%) compared to Black/African American (50.88%) or White (46.55%) patients (p = 0.255). Compared to White patients, Black/African American patients had worse overall survival (OS) probability (HR: 2.12, 95% CI: 1.46-3.1), while Asian patients did not have a significant difference (HR: 1.65, 95% CI: 0.98-2.8). Median OS was not reached, 59, and 37 months for White, Asian, and Black/African American patients, respectively. Measurable residual disease (MRD) percentage at the end of the first course of treatment varied significantly by race (median: 0, 0, 0.12% in White, Black/African American, Asian, respectively, p = 0.0064). Among cytogenetic abnormalities, t(6;11)(q27;q23) (p = 0.0022) and t(8;21) (p = 0.0059) were most enriched in Black/African American patients (n = 6, 5.26%, n = 23, 20.18%) compared with White (n = 9, 1.29%, n = 82, 11.78%) and Asian patients (n = 1, 2.08%; n = 6, 12.5%) p = 0.0022). In contrast, inv(16) occurred most frequently in White patients (n = 100, 14.34%) compared with Black/African American (n = 10, 8.77%) and Asian patients (n = 1, 2.08%; p = 0.0029). FLT3-ITD positivity was the highest in Asian patients (n = 14, 28.57%), followed by White (n = 134, 18.16%) and Black/African American patients (n = 9, 7.96%, p = 0.0039). Conclusion: Our findings highlight race-associated clinical variability in outcomes and cytogenetic attributes across pediatric AML patients. Black/African American patients had worse outcomes and more adverse-risk lesions. These patterns show that, beyond socioeconomic factors, potential underlying biological heterogeneity may contribute to racial disparities in AML outcomes and warrant further ancestry-driven investigations.