Triple-hit explanation for the worse prognosis of pediatric acute lymphoblastic leukemia among Mexican and Hispanic children

Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignancy among Mexican and Hispanic children and the first cause of death by disease in Mexico. We propose a “triple-hit” explanation for the survival gap affecting this population. The first hit can be attributed to epidemiology and social, cultural, and economic burdens. The second hit refers to cancer biology, with a high incidence of unfavorable genetic characteristics associated with an unfavorable response to treatment and, subsequently, poor survival. Finally, the third hit relates to sub-optimal treatment and support. Society and culture, leukemia biology, and treatment approach limitations are key factors that should not be seen apart and must be considered comprehensively in any strategy to improve the prognosis of Mexican and Hispanic children with ALL.

Securing access to a comprehensive diagnostic panel for children with suspected acute lymphoblastic leukemia: Results from the Mexico in Alliance with St. Jude “Bridge Project”

“…We also observed a higher frequency of iAMP21 (8.5%) in Mexicans, compared to Hispanics (1%) and Non-Hispanics (2%) ( 36 , 37 ) and a higher frequency of t(1;19)/EA2-PBX1 (7.5%) compared to baseline studies in Non-Hispanics (5%) ( 38 ). EA2-PBX1 and iAMP21 findings are consistent with prior reports in Mexican patients, where EA2-PBX1 has been identified in 7.2% of patients and iAMP21 in up to 10% of patients ( 35 ). Our observed frequencies for t(4;11)/KMT2A and t(9;22)/BCR-ABL (4.2% and 3.2%, respectively) are consistent with the literature for all three ethnicities ( 36 , 39 ).…”

“…Our observed frequencies for t(4;11)/KMT2A and t(9;22)/BCR-ABL (4.2% and 3.2%, respectively) are consistent with the literature for all three ethnicities ( 36 , 39 ). Finally, our observed frequency of hypodiploidy by IDNA (1.6%) is lower than reported in Mexican series, but consistent with the reported frequency in Hispanics and Non-Hispanics in the United States (1 and 2%), respectively ( 35 , 36 ).…”

“…Through the Bridge Project, we also documented the frequency of classic molecular alterations in a larger sample of Mexican children with ALL than in past studies, which have historically included 53-298 Mexican nationals ( 35 ). Consistent with the literature, we observed a lower frequency of t(12;21)/ETV6-RUNX1 compared to non-Hispanics (15.0% in our cohort, compared to 8.4-14.9% in other Mexican and Hispanic cohorts and 24% in Non-Hispanic cohorts) in the United States ( 35 ).…”

“…Through the Bridge Project, we also documented the frequency of classic molecular alterations in a larger sample of Mexican children with ALL than in past studies, which have historically included 53-298 Mexican nationals ( 35 ). Consistent with the literature, we observed a lower frequency of t(12;21)/ETV6-RUNX1 compared to non-Hispanics (15.0% in our cohort, compared to 8.4-14.9% in other Mexican and Hispanic cohorts and 24% in Non-Hispanic cohorts) in the United States ( 35 ). We also observed a higher frequency of iAMP21 (8.5%) in Mexicans, compared to Hispanics (1%) and Non-Hispanics (2%) ( 36 , 37 ) and a higher frequency of t(1;19)/EA2-PBX1 (7.5%) compared to baseline studies in Non-Hispanics (5%) ( 38 ).…”

A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children

“… 1 , 3 Moreover, Hispanic/Latino patients with ALL have lower overall survival compared to non-Hispanic White patients, even after accounting for social determinants of health. 4 , 5 , 6 Intriguingly, the disparity in ALL incidence appears to be principally attributable to the B cell ALL immunophenotype, 7 , 8 suggesting the possibility of specific underlying biological mechanisms.…”