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A RAG driver on the road to pediatric ALL

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Genomic aberrations affecting genes in B cell differentiation are hallmarks of B-precursor acute lymphoblastic leukemia (ALL). A new whole-genome sequencing study of ETV6-RUNX1–positive ALL has now identified RAG-mediated recombination, which specifically targets genes and regulatory elements active during B cell differentiation, as the underlying mechanism.

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Figure 1: Off-target RAG-mediated recombination in ETV6-RUNX1–positive ALL predominantly occurs at RSS-like motifs (gray triangles) in accessible, H3K4me3-marked (yellow pentagons) open chromatin.

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Authors and Affiliations

  1. Roland P. Kuiper and Esmé Waanders are affiliated with the Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands, and with the Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.,

    Roland P Kuiper & Esmé Waanders

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  1. Roland P Kuiper
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  2. Esmé Waanders
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Correspondence to Roland P Kuiper.

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The authors declare no competing financial interests.

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Kuiper, R., Waanders, E. A RAG driver on the road to pediatric ALL. Nat Genet 46, 96–98 (2014). https://doi.org/10.1038/ng.2879

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