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Clonal evolution of acute leukemia genomes

Oncogene volume 32, pages 135–140 (2013)Cite this article

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Abstract

In large part, cancer results from the accumulation of multiple mutations in a single cell lineage that are sequentially acquired and subject to an evolutionary process where selection drives the expansion of more fit subclones. Owing to the technical challenge of distinguishing and isolating distinct cancer subclones, many aspects of this clonal evolution are poorly understood, including the diversity of different subclones in an individual cancer, the nature of the subclones contributing to relapse, and the identity of pre-cancerous mutations. These issues are not just important to our understanding of cancer biology, but are also clinically important given the need to understand the nature of subclones responsible for the refractory and relapsed disease that cause significant morbidity and mortality in patients. Recently, advanced genomic techniques have been used to investigate clonal diversity and evolution in acute leukemia. Studies of pediatric acute lymphoblastic leukemia (ALL) demonstrated that in individual patients there are multiple genetic subclones of leukemia-initiating cells, with a complex clonal architecture. Separate studies also investigating pediatric ALL determined that the clonal basis of relapse was variable and complex, with relapse often evolving from a clone ancestral to the predominant de novo leukemia clone. Additional studies in both ALL and acute myeloid leukemia have identified pre-leukemic mutations in some individual cases. This review will highlight these recent reports investigating the clonal evolution of acute leukemia genomes and discuss the implications for clinical therapy.

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Acknowledgements

We would like to acknowledge Ryan Corces-Zimmerman for critical review of the manuscript. MJ is supported by the Lucille P Markey Biomedical Research Fellowship and the National Science Foundation Graduate Research Fellowship. RM holds a career award for medical scientists from the Burroughs Wellcome Fund.

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology, Cancer Institute, Stanford University School of Medicine, Palo Alto, CA, USA

    M Jan & R Majeti

  2. Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Palo Alto, CA, USA

    M Jan & R Majeti

  3. Program in Cancer Biology, Cancer Institute, Stanford University School of Medicine, Palo Alto, CA, USA

    M Jan & R Majeti

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Jan, M., Majeti, R. Clonal evolution of acute leukemia genomes. Oncogene 32, 135–140 (2013). https://doi.org/10.1038/onc.2012.48

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