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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, 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.

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  • Tumor suppressor BTG1 limits activation

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DOI

  • Esther Tijchon
  • Liesbeth van Emst
  • Laurensia Yuniati
  • Dorette van Ingen Schenau
  • Mylène Gerritsen
  • Laurens T van der Meer
  • Owen Williams
  • Peter M Hoogerbrugge
  • Blanca Scheijen
  • Frank N van Leeuwen

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.

Original languageEnglish
Pages (from-to)57-62.e3
Number of pages6
JournalExperimental Hematology
Volume60
Publication statusPublished - Apr-2018
Externally publishedYes

    Keywords

  • Journal Article, RUNX1, P53, ACUTE LYMPHOBLASTIC-LEUKEMIA, CHILDHOOD LEUKEMIA, MYELOID-LEUKEMIA, FUSION PROTEIN, DIFFERENTIATION, METHYLATION, ORIGINS, PRMT1

ID: 56045770