Journal article
Impact of Genetic Ancestry on Genomics and Survival Outcomes in T-cell Acute Lymphoblastic Leukemia
Blood cancer discovery, v 6(5)
28 May 2025
PMID: 40434808
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- Impact of Genetic Ancestry on Genomics and Survival Outcomes in T-cell Acute Lymphoblastic Leukemia
- Creators
- Haley Newman - Children's Hospital of PhiladelphiaShawn H R Lee - National University HospitalPetri Pölönen - St. Jude Children's Research HospitalRawan Shraim - Children's Hospital of PhiladelphiaYimei Li - Children's Hospital of PhiladelphiaHongyan Liu - Children's Hospital of PhiladelphiaRichard Aplenc - Children's Hospital of PhiladelphiaShovik Bandyopadhyay - University of PennsylvaniaChangya Chen - Children's Hospital of PhiladelphiaMeenakshi Devidas - St. Jude Children's Research HospitalCaroline Diorio - Children's Hospital of PhiladelphiaKimberly Dunsmore - University of Virginia Medical CenterOmar Elghawy - University of PennsylvaniaAmira Elhachimi - Children's Hospital of PhiladelphiaTori Fuller - Children's Hospital of PhiladelphiaSumit Gupta - Hospital for Sick ChildrenJunior Hall - Children's Hospital of PhiladelphiaAndrew D Hughes - Children's Hospital of PhiladelphiaStephen P Hunger - Children's Hospital of PhiladelphiaMignon L Loh - Seattle Children's HospitalZachary Martinez - Children's Hospital of PhiladelphiaMichael F McCoy - Children's Hospital of PhiladelphiaCassidy G Mullen - Children's Hospital of PhiladelphiaStanley B Pounds - St. Jude Children's Research HospitalElizabeth Raetz - NYU Langone HealthAnna Eames Seffernick - St. Jude Children's Research HospitalGongping Shi - Children's Hospital of PhiladelphiaJonathan Sussman - University of PennsylvaniaKai Tan - Children's Hospital of PhiladelphiaLahari Uppuluri - Children's Hospital of PhiladelphiaTiffaney L Vincent - Children's Hospital of PhiladelphiaRuth Wang'ondu - St. Jude Children's Research HospitalLena E Winestone - UCSF Benioff Children's HospitalStuart S Winter - Children's MinnesotaBrent L Wood - Children's Hospital of Los AngelesGang Wu - St. Jude Children's Research HospitalJason Xu - California University of PennsylvaniaWenjian Yang - St. Jude Children's Research HospitalCharles G Mullighan - St. Jude Children's Research HospitalJun J Yang - St. Jude Children's Research HospitalKira Bona - Dana-Farber/Boston Children's Cancer and Blood Disorders CenterDavid T Teachey - Children's Hospital of Philadelphia
- Publication Details
- Blood cancer discovery, v 6(5)
- Publisher
- AMER ASSOC CANCER RESEARCH; PHILADELPHIA
- Number of pages
- 13
- Grant note
- Gabriella Miller Kids FirstAlex's Lemonade Stand FoundationLeukemia and Lymphoma SocietySingapore National Medical Research CouncilSingapore National University Health System Clinician Scientist ProgrammeHyundai Hope on WheelsSt. Baldrick's Research FoundationPennsylvania Department of HealthHarrison Willing Memorial Research FundInvisible Prince FoundationAmerican Lebanese and Syrian Associated Charities of St. Jude Children's Research HospitalAiden Everett Davies Innovation FundSt Jude Chromatin CollaborativeCanadian Institute for Health Research
We are grateful for the editorial support of Barclay Lee of the Editorial Support Program at the Dana-Farber Cancer Institute. The details of funding/support are as follows: K12CA076931-24 (H. Newman and C. Diorio), Gabriella Miller Kids First X01HD100702 (D.T. Teachey, C.G. Mullighan, P. Poeloenen, M.L. Loh, S.P. Hunger, S.S. Winter, E. Raetz, B.L. Wood, M. Devidas, S.B. Pounds, K. Dunsmore, and J.J. Yang), R03CA256550 (D.T. Teachey, C.G. Mullighan, P. Poeloenen, M.L. Loh, S.P. Hunger, S.S. Winter, E. Raetz, B.L. Wood, M. Devidas, S.B. Pounds, K. Dunsmore, and J.J. Yang), Alex's Lemonade Stand Foundation (D.T. Teachey, K. Tan, S.P. Hunger, and C. Diorio), the Leukemia and Lymphoma Society (D.T. Teachey), Singapore National Medical Research Council (S.H.R. Lee), Singapore National University Health System Clinician Scientist Programme (S.H.R. Lee), Hyundai Hope on Wheels (D.T. Teachey, K. Tan, and R. Shraim), R01CA193776 (D.T. Teachey, B.L. Wood, K. Tan, C.G. Mullighan, S.P. Hunger, J.J. Yang, R. Shraim, and M. Devidas), U10CA180886 (D.T. Teachey and M.L. Loh), R01CA264837 (D.T. Teachey, J.J. Yang, C.G. Mullighan, K. Tan, B.L. Wood, and R. Shraim), U24CA114766 (D.T. Teachey, and M.L. Loh), U24CA196173 (D.T. Teachey), U10CA180899 (D.T. Teachey), St. Baldrick's Research Foundation (D.T. Teachey), Pennsylvania Department of Health (D.T. Teachey), the Harrison Willing Memorial Research Fund (D.T. Teachey), The Invisible Prince Foundation (D.T. Teachey), the Aiden Everett Davies Innovation Fund (D.T. Teachey), American Lebanese and Syrian Associated Charities of St. Jude Children's Research Hospital (C.G. Mullen), The St Jude Chromatin Collaborative (C.G. Mullen), P30CA021765 (C.G. Mullen), R35CA197695 (C.G. Mullen), U54CA243124 (C.G. Mullen), and the Canadian Institute for Health Research (C. Diorio). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001564194800003
- Scopus ID
- 2-s2.0-105015564299
- Other Identifier
- 991022054404804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Hematology
- Oncology