Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia

Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11464-9. doi: 10.1073/pnas.96.20.11464.


A large fraction of pediatric pre-B acute lymphoblastoid leukemias (ALL) consistently contain a t(1;19) chromosomal translocation. The t(1;19) translocation results in the production of a chimeric transcription factor containing the N-terminal transactivation domain of E2A fused to the C-terminal DNA-binding homeodomain of Pbx1. Here, we show that the E2A-Pbx1 fusion protein activates the expression of a novel WNT gene, WNT-16. WNT-16 normally is expressed in peripheral lymphoid organs such as spleen, appendix, and lymph nodes, but not in bone marrow. In contrast, high levels of WNT-16 transcripts are present in bone marrow and cell lines derived from pre-B ALL patients carrying the E2A-Pbx1 hybrid gene. Inhibition of E2A-Pbx1 expression leads to a significant decrease in WNT-16 mRNA levels, suggesting that WNT-16 is a downstream target of E2A-Pbx1. Three putative WNT receptors, FZ-2, FZ-3, and FZ-5, are expressed in cells of the B lineage, including pre-B ALL cells aberrantly expressing WNT-16. We propose that a WNT-16-mediated autocrine growth mechanism contributes to the development of t(1;19) pre-B ALL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Gene Expression Regulation
  • Homeodomain Proteins / physiology*
  • Humans
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion / physiology*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Transcription Factors / physiology*
  • Tumor Cells, Cultured
  • Wnt Proteins
  • Zebrafish Proteins*


  • Homeodomain Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • E2A-Pbx1 fusion protein

Associated data

  • GENBANK/AF169963
  • GENBANK/AF169964
  • GENBANK/AF172064
  • GENBANK/AH008358