Tumor suppressor BTG1 limits activation of BCL6 expression downstream of ETV6-RUNX1Tijchon, E., van Emst, L., Yuniati, L., van Ingen Schenau, D., Gerritsen, M., van der Meer, L. T., Williams, O., Hoogerbrugge, P. M., Scheijen, B. & van Leeuwen, F. N., Apr-2018, In : Experimental Hematology. 60, p. 57-62.e3 6 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||6|
|Publication status||Published - Apr-2018|
- Journal Article, RUNX1, P53, ACUTE LYMPHOBLASTIC-LEUKEMIA, CHILDHOOD LEUKEMIA, MYELOID-LEUKEMIA, FUSION PROTEIN, DIFFERENTIATION, METHYLATION, ORIGINS, PRMT1