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Genomic Analysis of the Clonal Origins of Relapsed Acute Lymphoblastic Leukemia
Open accessAbstract
Most children with acute lymphoblastic leukemia (ALL) can be cured, but the prognosis is dismal for the minority of patients who relapse after treatment. To explore the genetic basis of relapse, we performed genome-wide DNA copy number analyses on matched diagnosis and relapse samples from 61 pediatric patients with ALL. The diagnosis and relapse samples typically showed different patterns of genomic copy number abnormalities (CNAs), with the CNAs acquired at relapse preferentially affecting genes implicated in cell cycle regulation and B cell development. Most relapse samples lacked some of the CNAs present at diagnosis, which suggests that the cells responsible for relapse are ancestral to the primary leukemia cells. Backtracking studies revealed that cells corresponding to the relapse clone were often present as minor subpopulations at diagnosis. These data suggest that genomic abnormalities contributing to ALL relapse are selected for during treatment, and they point to new targets for therapeutic intervention.
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Cited by
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Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
Ding, L., Ley, T. J., Larson, D. E., Miller, C. A., Koboldt, D. C., Welch, J. S., Ritchey, J. K., Young, M. A., Lamprecht, T., McLellan, M. D., et al. (2012) · Nature · doi:10.1038/nature10738 · Cited by 1,993
Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia
Shlush, L. I., Zandi, S., Mitchell, A., Chen, W. C., Brandwein, J. M., Gupta, V., Kennedy, J. A., Schimmer, A. D., Schuh, A. C., Yee, K. W., et al. (2014) · Nature · doi:10.1038/nature13038 · Cited by 1,443
Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia
Mullighan, C. G., Su, X., Zhang, J., Radtke, I., Phillips, L. A. A., Miller, C. B., Ma, J., Liu, W., Cheng, C., Schulman, B. A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808253 · Cited by 1,422
Self-citationEvolution and impact of subclonal mutations in chronic lymphocytic leukemia
Landau, D. A., Carter, S. L., Stojanov, P., McKenna, A., Stevenson, K., Lawrence, M. S., Sougnez, C., Stewart, C., Sivachenko, A., Wang, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.019 · Cited by 1,379
Metadata
- Authors
- Mullighan, C. G., Phillips, L. A., Su, X., Ma, J., Miller, C. B., Shurtleff, S. A., & Downing, J. R.
- Venue
- Science
- Published
- 2008-11-28
- Volume
- 322
- Issue
- 5906
- Pages
- 1377-1380
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2060383229
- Cited by
- 806
- References
- 0
- FWCI
- 47.11
- Type
- journal article
- Language
- en
- Open access
- green
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- Mullighan, C. G., Phillips, L. A., Su, X., Ma, J., Miller, C. B., Shurtleff, S. A., & Downing, J. R. (2008). Genomic Analysis of the Clonal Origins of Relapsed Acute Lymphoblastic Leukemia. Science. https://doi.org/10.1126/science.1164266
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