BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition.
Nature
; 473(7347): 384-8, 2011 May 19.
Article
in En
| MEDLINE
| ID: mdl-21593872
ABSTRACT
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fusion Proteins, bcr-abl
/
Drug Resistance, Neoplasm
/
Protein Kinase Inhibitors
/
DNA-Binding Proteins
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nature
Year:
2011
Type:
Article
Affiliation country:
United States