Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
1999-10-13
pubmed:databankReference
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4920-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10490826-Adenomatous Polyposis Coli Protein, pubmed-meshheading:10490826-Amino Acid Sequence, pubmed-meshheading:10490826-B-Lymphocytes, pubmed-meshheading:10490826-Bone Marrow Cells, pubmed-meshheading:10490826-Cell Line, pubmed-meshheading:10490826-Cell Transformation, Neoplastic, pubmed-meshheading:10490826-Cytoskeletal Proteins, pubmed-meshheading:10490826-Expressed Sequence Tags, pubmed-meshheading:10490826-Fetus, pubmed-meshheading:10490826-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10490826-Homeodomain Proteins, pubmed-meshheading:10490826-Humans, pubmed-meshheading:10490826-Molecular Sequence Data, pubmed-meshheading:10490826-Neoplasm Proteins, pubmed-meshheading:10490826-Oncogene Proteins, Fusion, pubmed-meshheading:10490826-Organ Specificity, pubmed-meshheading:10490826-Phosphotyrosine, pubmed-meshheading:10490826-Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:10490826-Protein-Tyrosine Kinases, pubmed-meshheading:10490826-RNA, Messenger, pubmed-meshheading:10490826-Sequence Homology, Amino Acid, pubmed-meshheading:10490826-Signal Transduction, pubmed-meshheading:10490826-Stem Cells, pubmed-meshheading:10490826-Transcriptional Activation, pubmed-meshheading:10490826-Translocation, Genetic
pubmed:year
1999
pubmed:articleTitle
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.
pubmed:affiliation
Department of Pathology, University of California, San Diego, California, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.