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Science 28 November 2008:
Vol. 322. no. 5906, pp. 1377 - 1380
DOI: 10.1126/science.1164266
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Reports

Genomic Analysis of the Clonal Origins of Relapsed Acute Lymphoblastic Leukemia

Charles G. Mullighan,1 Letha A. Phillips,1 Xiaoping Su,1 Jing Ma,2 Christopher B. Miller,1 Sheila A. Shurtleff,1 James R. Downing1*

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.

1 Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2 Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

* To whom correspondence should be addressed. E-mail: james.downing{at}stjude.org

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