Document Detail

The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript.
MedLine Citation:
PMID:  3023859     Owner:  NLM     Status:  MEDLINE    
In the DNAs of all Ph1-positive chronic myelocytic leukemia patients studied to date, a breakpoint on chromosome 22 (the Ph1 chromosome) can be demonstrated with a probe from the bcr (breakpoint cluster region). Although the K562 cell line was established from cells of a chronic myelocytic leukemia patient, we have been unable to detect the Ph1 chromosome by cytogenetic means. Employing a probe from the 5' region of bcr, we have cloned an amplified Ph1 breakpoint fragment from K562. This demonstrates that K562 contains multiple remnants of a Ph1 chromosome with a breakpoint within bcr and thus may serve as a model system for the study of Ph1-positive chronic myelocytic leukemia at a molecular level. The isolation of bcr cDNA sequences shows that parts of bcr encode a protein. Employing K562, we demonstrate the presence of an abnormally sized mRNA species hybridizing to c-abl and to a bcr cDNA probe, indicating the possible consequence of the Ph1 translocation on a transcriptional level in chronic myelocytic leukemia. The isolation and sequencing of a cDNA containing the breakpoint area of this mRNA provide further evidence for its chimeric structure. Cloning of large stretches of chromosomal DNA flanking bcr and c-abl sequences in K562 and identification of the exons participating in the formation of the chimeric mRNA shows that a splice of at least 99 kilobases is made to fuse the 3' bcr exon to the 5' c-abl exon. Furthermore two chimeric cDNAs were isolated containing chromosome 9 sequences that map 43.5 kilobases downstream from the K562 breakpoint. These chromosome 9 sequences neither hybridize to the 8.5-kilobase chimeric c-abl mRNA nor to normal c-abl mRNAs in Hela cells and probably represent incorrect splicing products present in the K562 cell line.
G Grosveld; T Verwoerd; T van Agthoven; A de Klein; K L Ramachandran; N Heisterkamp; K Stam; J Groffen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  6     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1986 Feb 
Date Detail:
Created Date:  1987-01-20     Completed Date:  1987-01-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  607-16     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/M13096;  M13097;  M13098;  M13099;  M19695;  M19696
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MeSH Terms
Amino Acid Sequence
Base Sequence
Cell Line
Chromosome Aberrations*
Chromosomes, Human, Pair 22*
Cloning, Molecular
DNA / metabolism
DNA Restriction Enzymes
Leukemia, Myeloid / genetics*
Nucleic Acid Hybridization
Transcription, Genetic*
Reg. No./Substance:
9007-49-2/DNA; EC 3.1.21.-/DNA Restriction Enzymes

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