Abstract
INTRODUCTION: DUX4 is rearranged and overexpressed in a subgroup of acute lymphoblastic leukemia (ALL) with B-precursor phenotype, with a favorable outcome. Even though characteristic gene expression signature as well as surface expression of CD2/CD371 could be a hallmark of DUX4-rearranged ALL, actual detection of DUX4 rearrangement is, however, largely dependent on whole transcriptome analysis due to the highly repetitive nature of DUX4 gene loci and insertion as the main mechanism of fusion gene formation. METHODS: Polymerase chain reactions (PCRs) with several combinations of multiplex primers located on DUX4 and IGH gene loci were used for the detection of DUX4::IGH, which represents more than 90% of DUX4 fusion. RESULTS: DUX4::IGH fusion was successfully detected in three out of 50 ALL cases analyzed by standard PCR, and these positive cases showed variable insertion of DUX4 into the IGH locus. In all patients, sequences of unknown origin were observed at the junction of DUX4 and IGH sequences, indicating the role of the V(D)J recombination mechanism in fusion gene formation. Although DUX4 is tandemly repeated at its locus, only a single copy of the DUX4 sequence was detected at the IGH locus in two of the three DUX4-rearranged ALL cases. As previously reported, both CD2 and CD371 were positive in all cases with DUX4::IGH fusion, suggesting that the combination of CD2 and CD371 could be a more reliable marker for detecting the presence of this fusion. CONCLUSIONS: Identification of DUX4::IGH fusion in ALL could be possible more easily by a simple multiplex PCR strategy.