High frequency of cryptic chromosomal rearrangements involving the LMO2 gene in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes resulting from the transformation of T-cell progenitors. Around half of T-ALL patients harbor recurrent cytogenetic alterations, including juxtaposition of strong promoters and enhancers located in the TCRB (chr. 7q34) or TCRA-TCRD (chr. 14q11) loci with a variety of oncogenic transcription factors, such as LIM-only domain (LMO) genes, LMO1 and LMO2 resulting in their aberrant expression. 3] LMO2 is activated via chromosomal translocations t(11;14)(p13;q11) or t(7;11)(q35;p13) and del(11)(p12p13) in T-ALL patients. 5 Interestingly, high LMO2 expression levels have also been reported in many T-ALL patients without these changes, suggesting that cryptic LMO2 rearrangements may exist in T-ALL. Recently, we identified LMO2 rearrangements in 5 of 26 (19.2%) T-ALL cell lines including two novel cryptic non-TCR chromosome translocations t(3;11)(q25;p13) and t(X;11)(q25;p13), respectively activating LMO2 by juxtaposition with MBNL1 and STAG2. This prompted us to investigate novel rearrangements involving LMO2 in primary samples from T-ALL patients using fluorescence in situ hybridization (FISH) with tilepath BAC/fosmid clones, array-comparative genomic hybridization (CGH), and next generation sequencing (NGS) techniques.