Hispanic and Latino families in the Americas suffer increased risk of acute lymphoblastic leukaemia (ALL) because of a mutation that can be traced back to at least 13,000 years ago, according to the findings of a major research project.
Children from Hispanic and Latino background have the greatest risk in the Americas of developing ALL, and a 40% greater risk than children from white, non-Hispanic families.
The project, reported in Cell Genomics, has pinpointed a variation that reduces the expression of the IKZF1 gene, which encodes for a protein Ikaros that enables B-cell development.
The researchers have linked this gene to Indigenous American ancestry. They studied ancient DNA samples from the 12,700-year-old body of a person found at the Anzick site, Montana, USA. This suggests the variation was present among the migrants who first entered the Americas, they say.
After that, the variation increased in frequency among people in the Americas. One possible explanation for this being that it protected the migrants against new infections – as the variant is linked to a strengthening of the immune system.
Children with the gene variant, located at SNP rs76880433, were found to be 1.44 times as likely to develop ALL as children without the variant. The variant is found in about 30% of people of Hispanic/Latino origin. The study included more than 65,000 children, including 1,878 Hispanic children and 318 East Asian children treated in California for ALL.
Study co-leader Professor Vikay Sankaran, of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, USA, said: “We were able to use genetic studies in diverse populations to identify this new risk factor that explains some of the population differences in ALL risk. I hope our work will ultimately pave the path towards preventing this disease.”
Dr Adam de Smith from the University of Southern California’s Keck School of Medicine, who is joint first author of the study, said: “Looking at all of this together, we think that the risk variant is reducing IKZF1 expression. By doing so, it’s keeping B-cells in a more immature state, which would increase ALL risk by giving the cells more chance to develop mutations that could eventually lead to overt leukemia.”
Source:
de Smith AJ, Wahlster L, Jeon S, Kachuri L, Black S, Langie J, Cato LD, Nakatsuka N, Chan TF, Xia G, Mazumder S, Yang W, Gazal S, Eng C, Hu D, Burchard EG, Ziv E, Metayer C, Mancuso N, Yang JJ, Ma X, Wiemels JL, Yu F, Chiang CWK, Sankaran VG. (2024) “A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.” Cell Genomics 26 March 2024, doi: 10.1016/j.xgen.2024.100526
Link: https://www.cell.com/cell-genomics/fulltext/S2666-979X(24)00068-5
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