EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1.

Abstract

The t(1;19) translocation of pre-B cell acute lymphocytic leukemia (ALL) produces E2a-Pbx1, a chimeric oncoprotein containing the transactivation domains of E2a joined to the homeodomain protein, Pbx1. E2a-Pbx1 causes T cell and myeloid leukemia in mice, blocks differentiation of cultured myeloid progenitors, and transforms fibroblasts through a mechanism accompanied by aberrant expression of tissue-specific and developmentally-regulated genes. Here we investigate whether aberrant gene expression also occurs specifically in the t(1;19)-containing subset of pre-B cell ALL in man. Two new genes, EB-1 and EB-2, as well as Caldesmon were transcriptionally activated in each of seven t(1;19) cell lines. EB-1 expression was extremely low in marrow from patients having pre-B ALL not associated with the t(1;19), and elevated more than 100-fold in marrow from patients with pre-B ALL associated with the t(1;19). Normal EB-1 expression was strong in brain and testis, the same tissues exhibiting the highest levels of PBX1 expression. EB-1 encodes a signaling protein containing a phosphotyrosine binding domain homologous to that of dNumb developmental regulators and two SAM domains homologous to those in the C-terminal tail of Eph receptor tyrosine kinases. We conclude that aberrant expression of tissue-specific genes is a characteristic of t(1;19) pre-B ALL, as was previously found in fibroblasts transformed by E2a-Pbx1. Potentially, EB-1 overexpression could interfere with normal signaling controlling proliferation or differentiation.

• Authors: X Fu, S McGrath, M Pasillas, S Nakazawa, M P Kamps
• Journal: Oncogene (Oncogene) Vol. 18 Issue 35 Pg. 4920-9 (Sep 02 1999) ISSN: 0950-9232 [Print] England
• PMID: 10490826 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adenomatous Polyposis Coli Protein
• Cytoskeletal Proteins
• Homeodomain Proteins
• Neoplasm Proteins
• Oncogene Proteins, Fusion
• RNA, Messenger
• E2A-Pbx1 fusion protein
• Phosphotyrosine
• Protein-Tyrosine Kinases

Topics

• Adenomatous Polyposis Coli Protein
• Amino Acid Sequence
• B-Lymphocytes (enzymology, metabolism, pathology)
• Bone Marrow Cells (metabolism)
• Cell Line
• Cell Transformation, Neoplastic (genetics, pathology)
• Cytoskeletal Proteins (chemistry, genetics)
• Expressed Sequence Tags
• Fetus (metabolism)
• Gene Expression Regulation, Neoplastic
• Homeodomain Proteins (genetics)
• Humans
• Molecular Sequence Data
• Neoplasm Proteins (analysis, genetics)
• Oncogene Proteins, Fusion (genetics)
• Organ Specificity
• Phosphotyrosine (metabolism)
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (enzymology, genetics, pathology)
• Protein-Tyrosine Kinases (chemistry, metabolism)
• RNA, Messenger (analysis, genetics)
• Sequence Homology, Amino Acid
• Signal Transduction
• Stem Cells (enzymology, metabolism, pathology)
• Transcriptional Activation
• Translocation, Genetic (genetics)