Impact of Genetic Ancestry on Genomics and Survival Outcomes in T-cell Acute Lymphoblastic Leukemia
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.
Authors
- Kai Tan (ORCID: https://orcid.org/0000-0002-9104-5567)
- Michael F. McCoy (ORCID: https://orcid.org/0000-0001-5215-2725)
- Mignon L. Loh (ORCID: https://orcid.org/0000-0003-4099-4700)
- Jason Xu (ORCID: https://orcid.org/0000-0002-9061-3593)
- Brent Lee Wood (ORCID: https://orcid.org/0000-0001-7414-3969)
- Yimei Li (ORCID: https://orcid.org/0000-0001-9067-6992)
- Stephen P. Hunger (ORCID: https://orcid.org/0000-0002-5492-3957)
- Elizabeth A. Raetz (ORCID: https://orcid.org/0000-0002-8547-1658)
- Shawn H.R. Lee (ORCID: https://orcid.org/0000-0002-7161-3782)
- David T. Teachey (ORCID: https://orcid.org/0000-0001-7373-8987)
- Zachary Martinez
- Gongping Shi (ORCID: https://orcid.org/0000-0001-8432-8553)
- Gang Wu (ORCID: https://orcid.org/0000-0002-1678-5864)
- Petri Pölönen (ORCID: https://orcid.org/0000-0001-6128-9985)
- Lahari Uppuluri (ORCID: https://orcid.org/0000-0002-7217-892X)
- Wenjian Yang (ORCID: https://orcid.org/0000-0002-7305-5649)
- Hongyan Liu (ORCID: https://orcid.org/0000-0002-5308-4362)
- Junior Hall
- Richard Aplenc (ORCID: https://orcid.org/0000-0001-7482-5644)
- Andrew D. Hughes (ORCID: https://orcid.org/0000-0002-1251-2404)
- Rawan Shraim (ORCID: https://orcid.org/0009-0005-5350-3386)
- Haley Newman (ORCID: https://orcid.org/0000-0002-3022-8052)
- Lena E. Winestone (ORCID: https://orcid.org/0000-0001-9982-1594)
- Changya Chen (ORCID: https://orcid.org/0000-0003-4421-2462)
- Charles Grenfell Mullighan (ORCID: https://orcid.org/0000-0002-1871-1850)
- Jun J. Yang (ORCID: https://orcid.org/0000-0002-0770-9659)
- Kimberly P. Dunsmore (ORCID: https://orcid.org/0000-0002-6631-5174)
- Shovik Bandyopadhyay (ORCID: https://orcid.org/0000-0003-3919-3914)
- Stanley Pounds (ORCID: https://orcid.org/0000-0002-9167-2114)
- Stuart S. Winter (ORCID: https://orcid.org/0000-0003-3583-7727)
- Anna Eames Seffernick (ORCID: https://orcid.org/0000-0003-0848-4604)
- Caroline Diorio (ORCID: https://orcid.org/0000-0002-8005-3836)
- Sumit Gupta (ORCID: https://orcid.org/0000-0003-1334-3670)
- Omar Elghawy (ORCID: https://orcid.org/0000-0002-0786-8035)
- Tiffaney L. Vincent (ORCID: https://orcid.org/0009-0004-6147-7088)
- Ruth Wang’ondu
- Meenakshi Devidas (ORCID: https://orcid.org/0000-0002-1099-3478)
- Kira O'Neil Bona (ORCID: https://orcid.org/0000-0001-5602-7059)
- Jonathan Sussman (ORCID: https://orcid.org/0000-0002-3057-3550)
- Amira Elhachimi
- Cassidy G. Mullen
- Thomas Fuller
Institutions
- St. Jude Children's Research Hospital (US)
- Children's Hospital of Philadelphia (US)
- Children's Hospital of Los Angeles (US)
- Harvard University (US)
- National University of Singapore (SG)
- Hospital for Sick Children (CA)
- California University of Pennsylvania (US)
- NYU Langone Health (US)
- National University Cancer Institute, Singapore (SG)
- University of Virginia Children's Hospital (US)
- Seattle Children's Hospital (US)
- Center for Cancer and Blood Disorders (US)
- Dana-Farber Cancer Institute (US)
- Children's Minnesota (US)
- University of Virginia Medical Center (US)
- UCSF Benioff Children's Hospital (US)
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2025-05-28
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0049
- Citations
- 4
- Primary Topic
- Acute Lymphoblastic Leukemia research
- Type
- article
- Field-Weighted Citation Impact
- 7.51