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Intergenic Splicing of MDS1 and EVI1 Occurs in Normal Tissues as well as in Myeloid Leukemia and Produces a New Member of the PR Domain Family

The EVI1 gene, located at chromosome band 3q26, is overexpressed in some myeloid leukemia patients with breakpoints either 5′of the gene in the t(3;3)(q21;q26) or 3′of the gene in the inv(3)(q21q26). EVI1 is also expressed as part of a fusion transcript with the transcription factor AML1 in the t(3;...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-02, Vol.93 (4), p.1642-1647
Main Authors: Fears, Scott, Mathieu, Carol, Zeleznik-Le, Nancy, Huang, Shi, Rowley, Janet D., Nucifora, Giuseppina
Format: Article
Language:English
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Summary:The EVI1 gene, located at chromosome band 3q26, is overexpressed in some myeloid leukemia patients with breakpoints either 5′of the gene in the t(3;3)(q21;q26) or 3′of the gene in the inv(3)(q21q26). EVI1 is also expressed as part of a fusion transcript with the transcription factor AML1 in the t(3;21)(q26;q22), associated with myeloid leukemia. In cells with t(3;21), additional fusion transcripts are AML1-MDS1 and AML1-MDS1-EVI1.MDS1 is located at 3q26 170-400 kb upstream (telomeric) of EVI1 in the chromosomal region in which some of the breakpoints 5′of EVI1 have been mapped. MDS1 has been identified as a single gene as well as a previously unreported exon(s) of EVI1. We have analyzed the relationship between MDS1 and EVI1 to determine whether they are two separate genes. In this report, we present evidence indicating that MDS1 exists in normal tissues both as a unique transcript and as a normal fusion transcript with EVI1, with an additional 188 codons at the 5′end of the previously reported EVI1 open reading frame. This additional region has about 40% homology at the amino acid level with the PR domain of the retinoblastoma-interacting zinc-finger protein RIZ. These results are important in view of the fact that EVI1 and MDS1 are involved in leukemia associated with chromosomal translocation breakpoints in the region between these genes.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.4.1642