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PMID: 7689231 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 16 ·1993-08-15 ·Pages 7884-8

Domer PH, Fakharzadeh SS, Chen CS, Jockel J, Johansen L, Silverman GA, Kersey JH, Korsmeyer SJ

Abstract

A chromosomal translocation, t(4;11)-(q21;q23), is associated with an aggressive mixed-lineage leukemia. A yeast artificial chromosome was used to clone the chromosomal breakpoint of this translocation in the RS4;11 cell line. The breakpoint sequences revealed an inverted repeat bordered by a consensus site for topoisomerase II binding and cleavage as well as chi-like elements. The der(11) chromosome encodes a fusion RNA and predicted chimeric protein between the 11q23 gene MLL and a 4q21 gene designated AF4. The sequence of the complete open reading frame for this fusion transcript reveals the MLL protein to have homology with DNA methyltransferase, the Drosophila trithorax gene product, and the "AT-hook" motif of high-mobility-group proteins. An alternative splice that deletes the AT-hook region of MLL was identified. AF4 is a serine- and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis.

Related Genes
AF4 MLL
MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Chromosome Mapping Chromosomes, Fungal Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 4 Cloning, Molecular DNA Topoisomerases, Type II/metabolism Humans Leukemia/genetics Molecular Sequence Data Oligodeoxyribonucleotides Poly A/isolation & purification,metabolism RNA/isolation & purification,metabolism RNA, Messenger Recombinant Fusion Proteins/biosynthesis Repetitive Sequences, Nucleic Acid Restriction Mapping Saccharomyces cerevisiae/genetics Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Translocation, Genetic Tumor Cells, Cultured
Chemicals
Oligodeoxyribonucleotides RNA, Messenger Recombinant Fusion Proteins Poly A RNA DNA Topoisomerases, Type II
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Domer P H
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
Fakharzadeh S S
Chen C S
Jockel J
Johansen L
Silverman G A
Kersey J H
Korsmeyer S J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.16.7884
Published
1993-08-15
Pages
7884-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47247
Subset
IM
Databases
GENBANK
L22179
External Links
PubMed source DOI: 10.1073/pnas.90.16.7884 PMC Full Text View journal details
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