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].

BCR/ABL1 and BCR are under the transcriptional control of the MYC oncogene

SHARMA, NITESH DEVINARAYAN
Primo
;
MAGISTRONI, VERA
;
PIAZZA, ROCCO GIOVANNI;CITTERIO, STEFANIA;KHANDELWAL, PRAVEEN;GAMBACORTI PASSERINI, CARLO
Ultimo
2015

Abstract

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.
Articolo in rivista - Articolo scientifico
CML, BCR/ABL1, MYC
English
2015
14
1
132
reserved
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].
File in questo prodotto:
File Dimensione Formato  
BCR MYC MAX s12943-015-0407-0.pdf

Solo gestori archivio

Dimensione 2.75 MB
Formato Adobe PDF
2.75 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/121769
Citazioni
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 35
Social impact