IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia

Bruno A Lopes, Claus Meyer, Thayana C Barbosa, Caroline P Poubel, Marcela B Mansur, Nicolas Duployez, Matthew Bashton, Christine J. Harrison, Udo Zur Stadt, Martin Horstmann, Maria S Pombo-de-Oliveira, Chiara Palmi, Gianni Cazzaniga, Nicola C Venn, Rosemary Sutton, Cristina N Alonso, Grigory Tsaur, Sanjeev K Gupta, Sameer Bakhshi, Rolf MarschalekMariana Emerenciano

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6 Citations (Scopus)
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IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial deletions (53%). The latter included COBL-r, which were found in 12% of the IKZF1 ∆1-8 cohort. Patients with COBL-r are mostly classified as intermediate cytogenetic risk and frequently harbor ETV6, PAX5, CDKN2A/B deletions. Overall, 56% of breakpoints were located within COBL intron 5. Cryptic recombination signal sequence motifs were broadly distributed within the sequence of COBL, and no enrichment for the breakpoint cluster region was found. In summary, a diverse spectrum of alterations characterizes ΔIKZF1 and they also include deletion breakpoints within COBL. We confirmed that COBL is a hotspot associated with ΔIKZF1, but these rearrangements are not driven by RAG-mediated recombination.

Original languageEnglish
Pages (from-to)726-732
Number of pages7
JournalTranslational Oncology
Issue number5
Early online date13 Mar 2019
Publication statusPublished - 1 May 2019
Externally publishedYes


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