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.
SHARMA, N., MAGISTRONI, V., PIAZZA, R., CITTERIO, S., Mezzatesta, C., KHANDELWAL, P., et al. (2015). BCR/ABL1 and BCR are under the transcriptional control of the MYC oncogene. MOLECULAR CANCER, 14(1) [10.1186/s12943-015-0407-0].
|Citazione:||SHARMA, N., MAGISTRONI, V., PIAZZA, R., CITTERIO, S., Mezzatesta, C., KHANDELWAL, P., et al. (2015). BCR/ABL1 and BCR are under the transcriptional control of the MYC oncogene. MOLECULAR CANCER, 14(1) [10.1186/s12943-015-0407-0].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||BCR/ABL1 and BCR are under the transcriptional control of the MYC oncogene|
|Autori:||SHARMA, N; MAGISTRONI, V; PIAZZA, R; CITTERIO, S; Mezzatesta, C; KHANDELWAL, P; Pirola, A; GAMBACORTI PASSERINI, C|
SHARMA, NITESH DEVINARAYAN (Primo)
MAGISTRONI, VERA (Corresponding)
GAMBACORTI PASSERINI, CARLO (Ultimo)
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1186/s12943-015-0407-0|
|Appare nelle tipologie:||01 - Articolo su rivista|