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Cancer genetics

Initially complex, always heterogeneous

Nature Reviews Genetics volume 12, pages 154–155 (2011)Cite this article

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Acute lymphoblastic leukaemia (ALL) is particularly amenable to studies of genetic subpopulations owing to the ease of single-cell analyses, its limited genomic instability and its variety of well-characterized, recurrent mutations. Anderson and colleagues studied samples of childhood ALL that have an ETV6–RUNX1 translocation and used fluorescence in situ hybridization to detect other mutations (driver mutations) that are known to be involved in the development of ALL. In a separate study, Notta and colleagues studied genome-wide copy number alterations (CNAs) in adult ALL cases with a BCR–ABL translocation. By analysing individual leukaemic cells in each sample population, both groups found that the leukaemia-initiating cell subpopulation (defined by cell surface markers or by serial xenotransplantation in mice) maintained a genetic heterogeneity that was similar to the population of leukaemia cells in the sample. This suggests that the linear clonal succession model of cancer evolution, in which cancers progress through single-cell clone bottlenecks, might be an oversimplification. The genetic heterogeneity and the branching evolutionary trajectories evident in the samples evoke a remarkably Darwinian perspective of the evolution of leukaemia-initiating cells.

Interestingly, a comparison of multiple leukaemia samples from individual patients during disease progression and post-treatment relapse revealed that shifts can occur in the dominance of the subclones, although the subclonal diversity is generally maintained.

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ORIGINAL RESEARCH PAPERS

  1. Anderson, K. et al. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature 469 356–361 (2011)

    Article  CAS  PubMed  Google Scholar 

  2. Notta, F. et al. Evolution of human BCR–ABL1 lymphoblastic leukaemia-initiating cells. Nature 469 362–367 (2011)

    Article  CAS  PubMed  Google Scholar 

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  1. Darren J. Burgess
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Burgess, D. Initially complex, always heterogeneous. Nat Rev Genet 12, 154–155 (2011). https://doi.org/10.1038/nrg2965

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