Home LiteratureArticle Details
PMID: 3540951 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Overlapping cDNA clones define the complete coding region for the P210c-abl gene product associated with chronic myelogenous leukemia cells containing the Philadelphia chromosome.

Mes-Masson AM, McLaughlin J, Daley GQ, Paskind M, Witte ON

Abstract

The Philadelphia chromosome, observed in greater than 90% of patients with chronic myelogenous leukemia, results from a reciprocal translocation between chromosomes 9 and 22. The translocation breakpoint on chromosome 9 occurs near the ABL gene and correlates with the production of a chronic myelogenous leukemia-specific 8.5-kilobase ABL-related mRNA species accompanied by a structurally altered ABL protein (P210c-abl). The N-terminal sequence of the protein is derived from the BCR gene on chromosome 22. We have isolated overlapping cDNA clones from the K-562 cell line corresponding to approximately 8.5 kilobases of mRNA and have sequenced 2550 nucleotides at the 5' end. Our results indicate that the 5' end of the 8.5-kilobase mRNA consists of greater than 400 nucleotides of noncoding sequence that are greater than 80% G + C rich. Based on our sequence analysis, we propose that initiation of translation occurs at nucleotide 471, such that the initial 927 amino acids of P210c-abl are derived from BCR sequences. Our cDNA clones thus define the complete coding sequences for the P210c-abl gene product.

MeSH Terms
Base Sequence Cell Line Cloning, Molecular DNA/genetics Humans Leukemia, Myeloid/genetics Philadelphia Chromosome Proto-Oncogene Proteins/genetics Proto-Oncogenes RNA, Messenger/genetics
Chemicals
Proto-Oncogene Proteins RNA, Messenger DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mes-Masson A M
McLaughlin J
Daley G Q
Paskind M
Witte O N
References (42)
42 references, click to expand
  1. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia.
    Nature. 1985 Jun 13-19;315(6020):550-4 PMID: 2989692
  2. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds.
    Proc Natl Acad Sci U S A. 1978 May;75(5):2458-62 PMID: 276884
  3. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22.
    Cell. 1984 Jan;36(1):93-9 PMID: 6319012
  4. Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes.
    Nucleic Acids Res. 1981 Oct 24;9(20):5233-52 PMID: 7301588
  5. Selection of initiation sites by eucaryotic ribosomes: effect of inserting AUG triplets upstream from the coding sequence for preproinsulin.
    Nucleic Acids Res. 1984 May 11;12(9):3873-93 PMID: 6328442
  6. A simple and very efficient method for generating cDNA libraries.
    Gene. 1983 Nov;25(2-3):263-9 PMID: 6198242
  7. Casein kinases--multipotential protein kinases.
    Curr Top Cell Regul. 1982;21:101-27 PMID: 6814825
  8. Altered transcription of the c-abl oncogene in K-562 and other chronic myelogenous leukemia cells.
    Science. 1984 Jul 6;225(4657):72-4 PMID: 6587568
  9. A transformation-defective mutant of Abelson murine leukemia virus lacks protein kinase activity.
    Proc Natl Acad Sci U S A. 1980 Aug;77(8):4993-7 PMID: 6254050
  10. Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration.
    Proc Natl Acad Sci U S A. 1985 Mar;82(6):1810-4 PMID: 3856862
  11. Pattern recognition in nucleic acid sequences. II. An efficient method for finding locally stable secondary structures.
    Nucleic Acids Res. 1982 Jan 11;10(1):265-78 PMID: 6174936
  12. Initiation of translation of the cauliflower mosaic virus genome from a polycistronic mRNA: evidence from deletion mutagenesis.
    EMBO J. 1984 Dec 1;3(12):2731-6 PMID: 16453575
  13. Activation of the c-abl oncogene by viral transduction or chromosomal translocation generates altered c-abl proteins with similar in vitro kinase properties.
    Mol Cell Biol. 1985 Jan;5(1):204-13 PMID: 4039028
  14. Structural organization of the bcr gene and its role in the Ph' translocation.
    Nature. 1985 Jun 27-Jul 3;315(6022):758-61 PMID: 2989703
  15. The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript.
    Mol Cell Biol. 1986 Feb;6(2):607-16 PMID: 3023859
  16. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes.
    Cell. 1986 Jan 31;44(2):283-92 PMID: 3943125
  17. Rapid similarity searches of nucleic acid and protein data banks.
    Proc Natl Acad Sci U S A. 1983 Feb;80(3):726-30 PMID: 6572363
  18. Philadelphia chromosome-negative chronic myelogenous leukaemia: a morphological reassessment.
    Br J Haematol. 1985 Jul;60(3):457-67 PMID: 3860249
  19. The role of protein phosphorylation in the hormonal control of enzyme activity.
    Eur J Biochem. 1985 Sep 16;151(3):439-48 PMID: 2992967
  20. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.
    Blood. 1975 Mar;45(3):321-34 PMID: 163658
  21. Altered transcription of an oncogene in chronic myeloid leukaemia.
    Lancet. 1984 Mar 17;1(8377):593-5 PMID: 6142307
  22. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene.
    Science. 1986 Jul 11;233(4760):212-4 PMID: 3460176
  23. The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid.
    Cell. 1982 Dec;31(2 Pt 1):465-74 PMID: 6297767
  24. Genomic diversity correlates with clinical variation in Ph'-negative chronic myeloid leukaemia.
    Nature. 1986 Mar 20-26;320(6059):281-3 PMID: 3007992
  25. Chromosome studies on normal and leukemic human leukocytes.
    J Natl Cancer Inst. 1960 Jul;25:85-109 PMID: 14427847
  26. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity.
    Cell. 1984 Jul;37(3):1035-42 PMID: 6204766
  27. Initiation of translation at internal AUG codons in mammalian cells.
    Nature. 1984 May 3-9;309(5963):82-5 PMID: 6717585
  28. Chromosome abnormalities in human leukemia.
    Annu Rev Genet. 1980;14:17-39 PMID: 7011172
  29. Molecular cloning of a cDNA encoding human antihaemophilic factor.
    Nature. 1984 Nov 22-28;312(5992):342-7 PMID: 6438528
  30. The human cellular abl gene product in the chronic myelogenous leukemia cell line K562 has an associated tyrosine protein kinase activity.
    Virology. 1985 Jan 30;140(2):230-8 PMID: 2982232
  31. Ph1-negative chronic granulocytic leukemia: a nonentity.
    Am J Clin Pathol. 1986 Feb;85(2):186-93 PMID: 3456194
  32. The Philadelphia chromosome: a model of cancer and molecular cytogenetics.
    Cancer Genet Cytogenet. 1986 Mar 15;21(2):129-46 PMID: 3004697
  33. Multiple expression of Ig lambda-chain encoding RNA species in murine plasmacytoma cells.
    J Immunol. 1981 Jun;126(6):2104-8 PMID: 6164720
  34. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information.
    Nucleic Acids Res. 1981 Jan 10;9(1):133-48 PMID: 6163133
  35. Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1807-11 PMID: 3513189
  36. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining.
    Nature. 1973 Jun 1;243(5405):290-3 PMID: 4126434
  37. Rapid DNA isolations for enzymatic and hybridization analysis.
    Methods Enzymol. 1980;65(1):404-11 PMID: 6246361
  38. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia.
    Nature. 1983 Nov 17-23;306(5940):239-42 PMID: 6316147
  39. Chronic myelogenous leukemia: recent advances.
    Blood. 1985 May;65(5):1039-47 PMID: 2581632
  40. c-abl Oncogene and chromosome 22 "bcr" juxtaposition in chronic myelogenous leukemia.
    N Engl J Med. 1985 May 23;312(21):1393-4 PMID: 3857461
  41. A new method for sequencing DNA.
    Proc Natl Acad Sci U S A. 1977 Feb;74(2):560-4 PMID: 265521
  42. Mutation of a termination codon affects src initiation.
    Mol Cell Biol. 1984 Sep;4(9):1738-46 PMID: 6092936
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
Published
1986-12-00
Pages
9768-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC387222
Subset
IM
Databases
GENBANK
M15025
Corrections
ErratumIn
-
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com