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. 2025 May 28.
doi: 10.1158/2643-3230.BCD-25-0049. Online ahead of print.

Impact of Genetic Ancestry on Genomics and Survival Outcomes in T-cell Acute Lymphoblastic Leukemia

Haley Newman  1 , Shawn H R Lee  2 , Petri Pölönen  3 , Rawan Shraim  1 , Yimei Li  4 , Hongyan Liu  4 , Richard Aplenc  1 , Shovik Bandyopadhyay  5 , Changya Chen  4 , Meenakshi Devidas  6 , Caroline Diorio  1 , Kimberly Dunsmore  7 , Omar Elghawy  5 , Amira Elhachimi  4 , Tori Fuller  4 , Sumit Gupta  8 , Junior Hall  4 , Andrew D Hughes  4 , Stephen P Hunger  1 , Mignon L Loh  9 , Zachary Martinez  4 , Michael F McCoy  10 , Cassidy G Mullen  4 , Stanley B Pounds  11 , Elizabeth Raetz  12 , Anna Eames Seffernick  6 , Gongping Shi  1 , Jonathan Sussman  5 , Kai Tan  1 , Lahari Uppuluri  4 , Tiffaney L Vincent  10 , Ruth Wang'ondu  6 , Lena E Winestone  13 , Stuart S Winter  14 , Brent L Wood  15 , Gang Wu  3 , Jason Xu  16 , Wenjian Yang  11 , Charles G Mullighan  3 , Jun J Yang  3 , Kira Bona  17 , David T Teachey  1
Affiliations

Impact of Genetic Ancestry on Genomics and Survival Outcomes in T-cell Acute Lymphoblastic Leukemia

Haley Newman et al. Blood Cancer Discov. .

Abstract

The influence of genetic ancestry on genomics in T-cell Acute Lymphoblastic Leukemia (T-ALL) has not been fully explored. We examined the impact of genetic ancestry on multi-omic alterations, survival outcomes, and risk stratification. Among 1309 children and young adults with T-ALL treated on the Children's Oncology Group trial AALL0434, the prognostic value of five commonly altered T-ALL genes varied by ancestry-including NOTCH1, which was associated with superior overall survival for patients of European ancestry but non-prognostic among patients of African ancestry. Integrating genetic ancestry with published T-ALL risk classifiers, we identified that a X01 Penalized Cox Regression classifier stratified patients regardless of ancestry, whereas a European multi-gene classifier misclassified patients of certain ancestries. Overall, 80% of patients harbored a genomic alteration in at least one gene with differential prognostic impact in an ancestry-specific manner. These data demonstrate the importance of incorporating genetic ancestry into genomic risk classification.

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Update of

  • Impact of Genetic Ancestry on T-cell Acute Lymphoblastic Leukemia Outcomes.
    Teachey D, Newman H, Lee S, Pölönen P, Shraim R, Li Y, Liu H, Aplenc R, Bandyopadhyay S, Chen C, Chen Z, Devidas M, Diorio C, Dunsmore K, Elghawy O, Elhachimi A, Fuller T, Gupta S, Hall J, Hughes A, Hunger S, Loh M, Martinez Z, McCoy M, Mullen C, Pounds S, Raetz E, Ryan T, Seffernick A, Shi G, Sussman J, Tan K, Uppuluri L, Vincent TL, Wang'ondu R, Winestone L, Winter S, Wood B, Wu G, Xu J, Yang W, Mullighan C, Yang J, Bona K. Teachey D, et al. Res Sq [Preprint]. 2024 Aug 16:rs.3.rs-4858231. doi: 10.21203/rs.3.rs-4858231/v1. Res Sq. 2024. Update in: Blood Cancer Discov. 2025 May 28. doi: 10.1158/2643-3230.BCD-25-0049. PMID: 39184069 Free PMC article. Updated. Preprint.

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