Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia

Jun J. Yang, Cheng Cheng, Meenakshi Devidas, Xueyuan Cao, Yiping Fan, Dario Campana, Wenjian Yang, Geoff Neale, Nancy J. Cox, Paul Scheet, Michael J. Borowitz, Naomi J. Winick, Paul L. Martin, Cheryl L. Willman, W. Paul Bowman, Bruce M. Camitta, Andrew Carroll, Gregory H. Reaman, William L. Carroll, Mignon LohStephen P. Hunger, Ching Hon Pui, William E. Evans, Mary V. Relling

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163 Scopus citations

Abstract

Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries1, not all children have benefited equally from this progress2. Ethnic differences in survival after childhood ALL have been reported in many clinical studies3-11, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians3-5. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important 4,12. Interrogating genome-wide germline SNP genotypes in an unselected large cohort of children with ALL, we observed that the component of genomic variation that co-segregated with Native American ancestry was associated with risk of relapse (P = 0.0029) even after adjusting for known prognostic factors (P = 0.017). Ancestry-related differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy, indicating that modifications to therapy can mitigate the ancestry-related risk of relapse.

Original languageEnglish (US)
Pages (from-to)237-241
Number of pages5
JournalNature genetics
Volume43
Issue number3
DOIs
StatePublished - Mar 1 2011

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ASJC Scopus subject areas

  • Genetics

Cite this

Yang, J. J., Cheng, C., Devidas, M., Cao, X., Fan, Y., Campana, D., Yang, W., Neale, G., Cox, N. J., Scheet, P., Borowitz, M. J., Winick, N. J., Martin, P. L., Willman, C. L., Bowman, W. P., Camitta, B. M., Carroll, A., Reaman, G. H., Carroll, W. L., ... Relling, M. V. (2011). Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. Nature genetics, 43(3), 237-241. https://doi.org/10.1038/ng.763