Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Feb;84(2):105–109. doi: 10.1111/j.1349-7006.1993.tb02840.x

Induction of BCR‐ABL Fusion Genes by in vitro X‐irradiation

Takashi Ito 1, Toshio Seyama 1, Terumi Mizuno 1, Tomonori Hayashi 1, Keisuke S Iwamoto 1, Kiyohiko Dohi 2, Nori Nakamura 1, Mitoshi Akiyama 1,✉
PMCID: PMC5919137  PMID: 8463127

Abstract

The Philadelphia chromosome consists of a reciprocal translocation between the ABL oncogene at chromosome 9q34 and the BCR gene at chromosome 22q1l, resulting in the expression of chimeric BCR‐ABL mRNAs specific to chronic myelogenous leukemia (CML). Presence of the fusion gene can be detected with high specificity and sensitivity by means of reverse transcription and polymerase chain reaction. Using this assay, it was possible to detect BCR‐ABL fusion genes induced among HL60 cells after 100 Gy of X‐irradiation in vitro. In total, five fusion gene transcripts were obtained among 108 cells examined. These fusion genes contained not only CML‐specific BCR‐ABL rearrangements, but also other forms of BCR‐ABL fusions. These latter genes had junctions of BCR exon 4/ABL exon 2 intervened by a segment of DNA of unknown origin, BCR exon 5/ABL exon 2, and BCR exon 4/ABL exon 2. The results appear to be direct evidence for the induction of the BCR‐ABL fusion gene by X‐irradiation. In terms of leukemogenesis, it appears that only those cells bearing certain CML‐related BCR‐ABL fusion genes are positively selected by virtue of a growth advantage in vivo.

Keywords: BCR‐ABL, CML, X‐irradiation, Ph1

Full Text

The Full Text of this article is available as a PDF (495.5 KB).

REFERENCES

  • 1. ) Nowell , P. C. and Hungerford , D. A.A minute chromosome in human chronic granulocytic leukemia . Science , 132 , 1497 ( 1960. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) de Klein , A. , van Kessel , A. G. , Grosveld , G. , Bartram , C. R. , Hagemeijer , A. , Bootsma , D. , Supurr , N. K. , Heisterkamp , N. , Groffen , J. and Stephenson , J. R.A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia . Nature , 300 , 765 – 767 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Heinsterkamp , N. , Stam , K. , Groffen , J. , de Klein , A. and Grosveld , G.Structural organization of the bcr gene and its role in the Ph1 translocation . Nature , 315 , 758 – 761 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Heinsterkamp , N. , Stephenson , J. R. , Groffen , J. , Hansen , P. F. , de Klein , A. , Bartram , C. R. and Grosveld , G.Localization of the c‐abl oncogene adjacent to a translocation break point in chronic myelocytic leukaemia . Nature , 306 , 239 – 242 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Bernards , A. , Rubin , C. M. , Westbrook , C. A. , Paskind , M. and Baltimore , D.The first intron in the human c‐abl gene is at least 200 kilobases long and is a target for translocations in chronic myelogenous leukemia . Mol. Cell. Biol. , 7 , 3231 – 3236 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Shitivelman , E. , Lifshitz , B. , Gale , R. P. , Roe , B. A. and Canaani , E.Alternative splicing of RNAs transcribed from the human abl gene and from the bcr‐abl fused gene . Cell , 47 , 277 – 284 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Ichimaru , M. , Tomonaga , M. , Amenomori , T. and Matsuo , T.Atomic bomb and leukemia . J. Radiat. Res. , 32 ( Suppl. ), 162 – 167 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Awa , A. A.Persistent chromosome aberrations in the somatic cells of A‐bomb survivors, Hiroshima and Nagasaki . J. Radiat. Res. , 32 ( Suppl. ), 265 – 274 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Sambrook , J. , Fritsch , E. F. and Maniatis , T. “ Molecular Cloning A Laboratory Manual ,” 2nd Ed. , p. 7.19 ( 1989. ). Cold Spring Harbor Laboratory; , New York . [Google Scholar]
  • 10. ) Shtivelman , E. , Lifshitz , B. , Gale , R. P. and Canaani , E.Fused transcript of abl and bcr genes in chronic myelogenous leukaemia . Nature , 315 , 550 – 554 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Lozzio , C. B. and Lozzio , B. B.Human chronic myelogenous leukemia cell‐line with positive Philadelphia chromosome . Blood , 45 , 321 – 334 ( 1975. ). [PubMed] [Google Scholar]
  • 12. ) Pegoraro , L. , Matera , L. , Ritz , J. , Levis , A. , Palumbo , A. and Biagini , G.Establishment of a Ph1‐positive human cell line (BV173) . J. Natl. Cancer Inst. , 70 , 447 – 453 ( 1983. ). [PubMed] [Google Scholar]
  • 13. ) Kubonishi , I. and Miyoshi , I.Establishment of Ph1 chromosome‐positive cell line from chronic myelogenous leukemia in blast crisis . Int. J. Cell Cloning , 1 , 105 – 117 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Collins , S. J. , Kubonish , I. , Miyoshi , I. and Groudine , M. T.Altered transcription of the c‐abl oncogene in K‐562 and other chronic myelogenous leukemia cells . Science , 225 , 72 – 74 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Collins , S. J. , Gallo , R. C. and Gallagher , R. E.Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture . Nature , 270 , 347 – 349 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Kelin , E. , Klein , G. , Nadkarni , J. S. , Nadkarni , J. J. , Wigzell , H. and Clifford , P.Surface IgM‐kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines . Cancer Res. , 28 , 1300 – 1310 ( 1968. ). [PubMed] [Google Scholar]
  • 17. ) Kawasaki , E. S. , Clark , S. S. , Coyne , M. Y. , Smith , S. D. , Champlin , R. , Witte , O. N. and McCormick , F. P.Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia‐specific mRNA sequences amplified in vitro . Proc. Natl. Acad. Sci. USA , 85 , 5698 – 5702 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Sanger , F. , Nicklen , S. and Coulson , A. R.DNA sequencing with chain‐terminating inhibitors . Proc. Natl. Acad. Sci. USA , 74 , 5463 – 5467 ( 1977. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Holmberg , M. and Jonasson , J.Preferential location of X‐ray induced chromosome breakage in the R‐bands of human chromosomes . Hereditas , 74 , 57 – 68 ( 1973. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Buckton , K. E.Identification with G and R banding of the position of breakage points induced in human chromosomes by in vitro X‐irradiation . Int. J. Radiat. Biol. , 29 , 475 – 488 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Roman , C. S. and Bobrow , M.The sites of radiationinduced breakage in human lymphocyte chromosomes, determined by quinacrine fluorescence . Mutat. Res. , 18 , 325 – 331 ( 1973. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Holmberg , M. and Carrano , A. V.Neutron induced break‐points in human chromosomes have a similar location as X‐ray induced break‐points . Hereditas , 89 , 183 – 187 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Haglund , U. , Lundell , G. , Zech , L. and Ohlin , J.Radioiodine administration in hyperthyroidism, a cytogenetic study . Hereditas , 87 , 85 – 98 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Franz , W. M. , Berger , P. and Wang , J. Y. J.Deletion of an N‐terminal regulatory domain of the c‐abl tyrosine kinase activates its oncogenic potential . EMBO J. , 8 , 137 – 147 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Lugo , T. G. , Pendergast , A. M. , Muller , A. J. and Witte , O. N.Tyrosine kinase activity and transformation potency of bcr‐abl oncogene products . Science , 247 , 1079 – 1082 ( 1990. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES