Journal article
Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations
Proceedings of the National Academy of Sciences - PNAS, Vol.89(24), pp.11794-11798
12/15/1992
Handle:
https://hdl.handle.net/2376/107611
PMCID: PMC50643
PMID: 1465401
Abstract
Recurring chromosomal abnormalities involving translocations at chromosome 11 band q23 are associated with human myeloid and lymphoid leukemia as well as lymphoma. We have identified the gene located at this break-point and have named it MLL (for myeloid-lymphoid, or mixed-lineage, leukemia). The t(4;11), t(6;11), t(9;11), and t(11;19) are among the most common reciprocal translocations in leukemia cells involving this chromosomal band. We now have evidence that the breakpoints in all of these translocations are clustered within a 9-kilobase (kb) BamHI genomic region of the MLL gene. By Southern blot hybridization using a 0.7-kb BamHI cDNA fragment of the MLL gene called MLL 0.7B, we have detected rearrangements of DNA from cell lines and patient material with an 11q23 translocation in this region. Northern blot analyses indicate that this gene has multiple transcripts, some of which appear to be lineage-specific. In normal pre-B cells, four transcripts of 12.5, 12.0, 11.5, and 2.0 kb are detected. These transcripts are also present in monocytoid cell lines with additional hybridization to a 5.0-kb transcript, indicating that expression of different-sized MLL transcripts may be associated with normal hematopoietic lineage development. In a cell line with a t(4;11), the expression of the 12.5-, 12.0-, and 11.5-kb transcripts is reduced, and there is evidence of three other altered transcripts of 11.5, 11.25, and 11.0 kb. Thus, these 11q23 translocations result in rearrangements of the MLL gene and may lead to altered function(s) of MLL and of other gene(s) involved in the translocation.
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Details
- Title
- Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations
- Creators
- N R McCabe - Department of Pediatrics, University of Chicago, IL 60637R C Burnett - Department of Pediatrics, University of Chicago, IL 60637H J Gill - Department of Pediatrics, University of Chicago, IL 60637M J Thirman - Department of Pediatrics, University of Chicago, IL 60637D Mbangkollo - Department of Pediatrics, University of Chicago, IL 60637M Kipiniak - Department of Pediatrics, University of Chicago, IL 60637E van Melle - Department of Pediatrics, University of Chicago, IL 60637S Ziemin-van der Poel - Department of Pediatrics, University of Chicago, IL 60637J D Rowley - Department of Pediatrics, University of Chicago, IL 60637M O Diaz - Department of Pediatrics, University of Chicago, IL 60637
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.89(24), pp.11794-11798
- Academic Unit
- Molecular Biosciences, School of
- Identifiers
- 99900547481901842
- Language
- English
- Resource Type
- Journal article