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© 1993 Oxford University Press

RESEARCH-ARTICLE

Characterization and chromosomal localization of the human proto-oncogene BMI-1

Mark Alkema, Joop Wiegant1, Anton K. Raap1, Anton Bems and Maarten van Lohuizen*

Division of Molecular Genetics and Department of Biochemistry University of Amsterdam, The Netherlands Cancer Institute Plesmanlaas 121. 1066 CX Amsterdam 1Department of Cytochemistry and Cytometry, University of Leiden 2333 AL Leiden, The Netherlands

*To whom correspondence should be addressed

Received June 22, 1993; Revised July 26, 1993; Accepted July 26, 1993

The proto-oncogene bml-1 is frequently activated by Moloney murine leukemia proviral insertions in Eµ-mcy transgenic mice1,2 Using a mouse bmi-1 cDNA probe a transcript of 3.3 kb was detected on Northern blots of human Burkitts lymphoma cell lines. We have Isolated and sequenced cDNA clones from a human erythroleukemia cell line (K562) derived cDNA library, using different mouse bml-l cDNA fragments as a probe. Analysis of genomic BMI-1 sequences reveals a gene structure which is very similar to that of the mouse, consisting of at least 10 exons. The human cDNA is 3203 bp in length and shows 86% identify to the mouse nucleotide sequence. The open reading frame encodes a protein of 326 amino acids which shares 98% Identity to the amino acid sequence of mouse bmi-1 protein. In vitro translation experiments show that human cDNA derived RNA translates into a protein with a mobility of 44–46 kD on SDS polyacrylamide gels. Fluorescence In situ hybridization (FISH) on metaphase chromosome spreads located the human BMI-1 gene to the short arm of chromosome 10 (10p13), a region known to be involved in translocations in various leukemias.


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