Abstract

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.

Keywords

clone (Java method)BiologySomatic evolution in cancerLymphoblastic LeukemiaGeneLeukemiaGenomeOncologyImmunologyGeneticsMedicine

Affiliated Institutions

Related Publications

Publication Info

Year
2008
Type
article
Volume
322
Issue
5906
Pages
1377-1380
Citations
802
Access
Closed

External Links

View on DOI.org

Social Impact

Altmetric
PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

802
OpenAlex

Cite This

Charles G. Mullighan, Letha A. Phillips, Xiaoping Su et al. (2008). Genomic Analysis of the Clonal Origins of Relapsed Acute Lymphoblastic Leukemia. Science , 322 (5906) , 1377-1380. https://doi.org/10.1126/science.1164266

Identifiers

DOI
10.1126/science.1164266