Contributions
Abstract: PB1623
Type: Publication Only
Background
DUX4 has recently been presented as new oncogenic driver in B cell acute lymphoblastic leukemia (pre B-ALL) of adolescents and young adults [1]. Translocations of DUX4, especially those with the IGH locus led to high expression of the corresponding fusion gene. DUX4 then triggered the expression or a novel isoform of the ETS transcription factor ERG in pre B-ALL [2]. Focal deletions of exons 3-9 were a second cause for short ERG variants. Up to 7% of pre B-ALL showed deregulated expression of both genes, DUX4 and ERG [2].
Aims
We set out to find pre B-ALL cell lines with DUX4 translocation and ERG deletion as potential model systems for this novel subtype of pre B-ALL.
Methods
We screened a panel of ALL cell lines for aberrant expression of DUX4 mRNA as potential indicator for DUX4 translocations. Genomic PCR was performed to detect focal ERG deletions, qRT-PCR showed expression of alternative ERG exon 6, transcriptional target of DUX4.
Results
Genomic PCR showed that 2/66 pre B-ALL cell lines (NALM-6, SUP-B15) tested carried deletions targeting ERG exon 5. Results of DUX4 qRT-PCR (Taqman probe Hs03037979_g1) were surprisingly inconsistent with Western blot analysis - which could only in part be explained by DUX4 being a one-exon gene. NALM-6 was the only cell line expressing the DUX4 protein. Likewise, the alternative ERG transcript with alternative exon 6 was observed in NALM-6 only.
Conclusion
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): B cell acute lymphoblastic leukemia, ALL
Abstract: PB1623
Type: Publication Only
Background
DUX4 has recently been presented as new oncogenic driver in B cell acute lymphoblastic leukemia (pre B-ALL) of adolescents and young adults [1]. Translocations of DUX4, especially those with the IGH locus led to high expression of the corresponding fusion gene. DUX4 then triggered the expression or a novel isoform of the ETS transcription factor ERG in pre B-ALL [2]. Focal deletions of exons 3-9 were a second cause for short ERG variants. Up to 7% of pre B-ALL showed deregulated expression of both genes, DUX4 and ERG [2].
Aims
We set out to find pre B-ALL cell lines with DUX4 translocation and ERG deletion as potential model systems for this novel subtype of pre B-ALL.
Methods
We screened a panel of ALL cell lines for aberrant expression of DUX4 mRNA as potential indicator for DUX4 translocations. Genomic PCR was performed to detect focal ERG deletions, qRT-PCR showed expression of alternative ERG exon 6, transcriptional target of DUX4.
Results
Genomic PCR showed that 2/66 pre B-ALL cell lines (NALM-6, SUP-B15) tested carried deletions targeting ERG exon 5. Results of DUX4 qRT-PCR (Taqman probe Hs03037979_g1) were surprisingly inconsistent with Western blot analysis - which could only in part be explained by DUX4 being a one-exon gene. NALM-6 was the only cell line expressing the DUX4 protein. Likewise, the alternative ERG transcript with alternative exon 6 was observed in NALM-6 only.
Conclusion
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): B cell acute lymphoblastic leukemia, ALL