ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis

Leukemia. 2022 Feb;36(2):549-554. doi: 10.1038/s41375-021-01409-9. Epub 2021 Sep 17.

Abstract

  1. ETV6-RUNX1 and RUNX1 directly promote RAG1 expression.

  2. ETV6-RUNX1 and RUNX1 preferentially bind to the −1200 bp enhancer of RAG1 and the −80 bp promoter of RAG1 gene respectively, and compete for these bindings.

  3. ETV6-RUNX1 and RUNX1 induce an excessive RAG recombinase activity.

  4. ETV6-RUNX1 participates directly in two events of the multi-hit ALL leukemogenesis: as an initiating event and as an activator of RAG1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Gene Expression Regulation, Leukemic*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Tumor Cells, Cultured

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Homeodomain Proteins
  • Oncogene Proteins, Fusion
  • RUNX1 protein, human
  • TEL-AML1 fusion protein
  • RAG-1 protein