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Background

Chronic Myeloid Leukaemia (CML) is caused by the BCR/ABL1 fusion gene. Both the presence and the levels of BCR/ABL1 expression seem to be critical for CML progression from chronic phase (CP) to blast crisis (BC). After the oncogenic translocation, the BCR/ABL1 gene is under the transcriptional control of BCR promoter but the molecular mechanisms involved in the regulation of oncogene expression are mostly unknown.

Methods

A region of 1443bp of the functional BCR promoter was studied for transcription factor binding sites through in-silico analysis and Chromatin Immunoprecipitation experiments. BCR and BCR/ABL1 expression levels were analysed in CML cell lines after over-expression or silencing of MYC transcription factor. A luciferase reporter assay was used to confirm its activity on BCR promoter.

Results

In the present study we demonstrate that MYC and its partner MAX bind to the BCR promoter, leading to up-regulation of BCR and BCR/ABL1 at both transcriptional and protein levels. Accordingly, silencing of MYC expression in various BCR/ABL1 positive cell lines causes significant downregulation of BCR and BCR/ABL1, which consequently leads to decreased proliferation and induction of cell death.

Conclusions

Here we describe a regulatory pathway modulating BCR and BCR/ABL1 expression, showing that the BCR promoter is under the transcriptional control of the MYC/MAX heterodimer. Since MYC is frequently over-expressed in BC, this phenomenon could play a critical role in BCR/ABL1 up-regulation and blast aggressiveness acquired during CML evolution."xsd:string
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http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/author"Sharma N."xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/author"Gambacorti-Passerini C."xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/author"Citterio S."xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/author"Piazza R."xsd:string
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http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/author"Magistroni V."xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/author"Pirola A."xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/author"Mezzatesta C."xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/name"Mol Cancer"xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/pages"132"xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/title"BCR/ABL1 and BCR are under the transcriptional control of the MYC oncogene."xsd:string
http://purl.uniprot.org/citations/26179066http://purl.uniprot.org/core/volume"14"xsd:string
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