Session: 603. Oncogenes and Tumor Suppressors: Poster III
Hematology Disease Topics & Pathways:
Diseases, Leukemia, ALL, AML, Technology and Procedures, Lymphoid Malignancies, Clinically relevant, Myeloid Malignancies, NGS
We have developed a customized NGS panel for MLL diagnostics to utilize state of the art technology at DCAL. With this new tool, the whole MLL gene is analyzed in contrast to the LDI-PCR where only the main MLL breakpoint cluster region (BCR-1) is covered. The first results of the NGS analysis of 84 patients identified MLL breakpoints located outside the main BCR-1 of MLL. Furthermore, a novel MLL partner gene USP2 was identified in 16 patients. All MLL-USP2 positive patients had a breakpoint located outside BCR-1 and within a newly defined breakpoint cluster region BCR-2. The BCR-2 site was also used in 2 other patients with MLL-AFF1 and one patient with MLL-MLLT3.
These findings reveal USP2 as a new entity for MLL rearrangements affecting indifferently children aged 3 months to 10 years old (mean 30 months) with no gender bias (M/F=1.3). Interestingly, only 5/16 affected children were below 1 year of age at diagnosis and thus treated according to the Interfant trial. Clinical presentation as well as outcome associated with this new entity deserves further investigation to define whether those patients should be allocated, as other MLL-rearranged ones, in high-risk treatment groups. More MLL patients should also be analyzed to get a better idea of the frequency of breakpoints within BCR-2, especially the frequency of MLL-USP2 fusions. Indeed, standard FISH analysis and CGH array do not permit reliable detection of this fusion, explaining why they remained undetected so far. The biology of this novel MLL rearrangement also deserves further investigation, considering that USP2 is the only MLL partner fused exclusively to BCR-2.
Disclosures: No relevant conflicts of interest to declare.
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