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Tumor suppressor BTG1 limits activation of BCL6 expression downstream of ETV6-RUNX1

Tijchon, E; van Emst, L; Yuniati, L; van Ingen Schenau, D; Gerritsen, M; van der Meer, LT; Williams, O; ... van Leeuwen, FN; + view all (2018) Tumor suppressor BTG1 limits activation of BCL6 expression downstream of ETV6-RUNX1. Experimental Hematology , 60 57-62.e3. 10.1016/j.exphem.2018.01.006. Green open access

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Abstract

Translocation t(12;21) (p13;q22), giving rise to the ETV6-RUNX1 fusion gene, is the most common genetic abnormality in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation usually arises in utero, but its expression is insufficient to induce leukemia and requires other cooperating genetic lesions for BCP-ALL to develop. Deletions affecting the transcriptional coregulator BTG1 are frequently observed in ETV6-RUNX1-positive leukemia. Here we report that Btg1 deficiency enhances the self-renewal capacity of ETV6-RUNX1-positive mouse fetal liver-derived hematopoietic progenitors (FL-HPCs). Combined expression of the fusion protein and a loss of BTG1 drive upregulation of the proto-oncogene Bcl6 and downregulation of BCL6 target genes, such as p19Arf and Tp53. Similarly, ectopic expression of BCL6 promotes the self-renewal and clonogenic replating capacity of FL-HPCs, by suppressing the expression of p19Arf and Tp53. Together these results identify BCL6 as a potential driver of ETV6-RUNX1-mediated leukemogenesis, which could involve loss of BTG1-dependent suppression of ETV6-RUNX1 function.

Type: Article
Title: Tumor suppressor BTG1 limits activation of BCL6 expression downstream of ETV6-RUNX1
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.exphem.2018.01.006
Publisher version: http://dx.doi.org/10.1016/j.exphem.2018.01.006
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10046750
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