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Intragenic  ERG  deletions occur in 3–5% of B-cell precursor acute lymphoblastic leukemia, specifically in B-other subtype lacking the classifying genetic lesions. They represent the only genetic lesion described so far present in the majority of cases clustering into a subgroup of B-other subtype characterized by a unique gene expression profile, probably sharing a common, however, not yet fully described, biological background. We aimed to elucidate whether  ERG  deletions could drive the specific biology of this  ERG -related leukemia subgroup through expression of aberrant or decreased expression of wild type  ERG  isoforms. We showed that leukemic cells with endogenous  ERG  deletion express an aberrant transcript translated into two proteins in transfected cell lines and that one of these proteins colocalizes with wild type ERG. However, we did not confirm expression of the proteins in acute lymphoblastic leukemia cases with endogenous  ERG  deletion.  ERG  deletions resulted in significantly lower expression of wild type ERG transcripts compared to B-other cases without  ERG  deletion. However, cases with subclonal  ERG  deletion, clustering to the same  ERG  deletion associated subgroup, presented similar levels of wild type  ERG  as cases without  ERG  deletion. In conclusion, our data suggest that neither the expression of aberrant proteins from internally deleted allele nor the reduced expression of wild type  ERG  seem to provide a plausible explanation of the specific biology of  ERG  -related leukemia subgroup.

Intragenic ERG Deletions Do Not Explain the Biology of ERG-Related Acute Lymphoblastic Leukemia