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 Loh; Stephen P. Hunger; Ching Hon Pui; William E. Evans; Mary V. Relling

doi:10.1038/ng.763

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

Pediatrics

Research output: Contribution to journal › Review article › peer-review

177 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 studies^3-11, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians^3-5. 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 language	English
Pages (from-to)	237-241
Number of pages	5
Journal	Nature Genetics
Volume	43
Issue number	3
DOIs	https://doi.org/10.1038/ng.763
State	Published - Mar 2011

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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

Yang, Jun J. ; Cheng, Cheng ; Devidas, Meenakshi ; Cao, Xueyuan ; Fan, Yiping ; Campana, Dario ; Yang, Wenjian ; Neale, Geoff ; Cox, Nancy J. ; Scheet, Paul ; Borowitz, Michael J. ; Winick, Naomi J. ; Martin, Paul L. ; Willman, Cheryl L. ; Bowman, W. Paul ; Camitta, Bruce M. ; Carroll, Andrew ; Reaman, Gregory H. ; Carroll, William L. ; Loh, Mignon ; Hunger, Stephen P. ; Pui, Ching Hon ; Evans, William E. ; Relling, Mary V. / Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. In: Nature Genetics. 2011 ; Vol. 43, No. 3. pp. 237-241.

@article{4a5f5db355e34d9db07623f84cb60096,

title = "Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia",

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.",

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

year = "2011",

month = mar,

doi = "10.1038/ng.763",

language = "English",

volume = "43",

pages = "237--241",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

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Yang, JJ, Cheng, C, Devidas, M, Cao, X, Fan, Y, Campana, D, Yang, W, Neale, G, Cox, NJ, Scheet, P, Borowitz, MJ, Winick, NJ, Martin, PL, Willman, CL, Bowman, WP, Camitta, BM, Carroll, A, Reaman, GH, Carroll, WL, Loh, M, Hunger, SP, Pui, CH, Evans, WE & Relling, MV 2011, 'Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia', Nature Genetics, vol. 43, no. 3, pp. 237-241. https://doi.org/10.1038/ng.763

Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. / Yang, Jun J.; Cheng, Cheng; Devidas, Meenakshi; Cao, Xueyuan; Fan, Yiping; Campana, Dario; Yang, Wenjian; Neale, Geoff; Cox, Nancy J.; Scheet, Paul; Borowitz, Michael J.; Winick, Naomi J.; Martin, Paul L.; Willman, Cheryl L.; Bowman, W. Paul; Camitta, Bruce M.; Carroll, Andrew; Reaman, Gregory H.; Carroll, William L.; Loh, Mignon; Hunger, Stephen P.; Pui, Ching Hon; Evans, William E.; Relling, Mary V.

In: Nature Genetics, Vol. 43, No. 3, 03.2011, p. 237-241.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia

AU - Yang, Jun J.

AU - Cheng, Cheng

AU - Devidas, Meenakshi

AU - Cao, Xueyuan

AU - Fan, Yiping

AU - Campana, Dario

AU - Yang, Wenjian

AU - Neale, Geoff

AU - Cox, Nancy J.

AU - Scheet, Paul

AU - Borowitz, Michael J.

AU - Winick, Naomi J.

AU - Martin, Paul L.

AU - Willman, Cheryl L.

AU - Bowman, W. Paul

AU - Camitta, Bruce M.

AU - Carroll, Andrew

AU - Reaman, Gregory H.

AU - Carroll, William L.

AU - Loh, Mignon

AU - Hunger, Stephen P.

AU - Pui, Ching Hon

AU - Evans, William E.

AU - Relling, Mary V.

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

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DO - 10.1038/ng.763

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JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

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Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia

Abstract

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