The interplay between IKZF1 and COBL deletions in leukemia

Background:

IKZF1 deletions (ΔIKZF1) are predictive for relapses in B-cell acute lymphoblastic leukemia (BCP-ALL). We previously revealed that Cordon-Bleu rearrangements (COBL-r) could promote ΔIKZF1. Here, we aim at characterizing COBL-r at the genomic level and to unravel its clinical importance.

Methods:

146 BCP-ALL were screened for ΔIKZF1 with SNP-array or MLPA P355/P202. Recurrent ΔIKZF1 were confirmed by multiplex (M)-PCR, and remaining samples were evaluated by MLPA followed by M- or LDI-PCR to identify the corresponding COBL-r.

Results:

Patients can be categorized into the following two groups: Δ1 – 8 (n = 109) or Δn-8 (n = 37). IKZF1 Δ1 – 8 were caused by monosomy 7 (18%), i(7q) (10%), 7 p loss (19%), 7 p interstitial deletions (41%), and ΔIKZF1 with COBL-r (12%). IKZF1 Δn-8 were recurrent deletions (86%), larger 7 p deletions (8%) or involving the COBL gene (6%). Overall, 10% of our cohort had COBL-r with breakpoints located either at the promoter (15%) or the gene-body (85%; mainly in COBL intron 5 (55%) or intron 7 (15%)).

Conclusion:

Diverse alterations characterize the molecular deletions within the IKZF1 gene in the investigated cohort of BCP-ALL patients, including a subgroup of patients (10%) that carry larger deletions comprising the IKZF1 and COBL genes, respectively.

This work is supported from the "Georg und Franziska Speyer'sche Hochschulstiftung".