Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model

F. E. Cotter, P. Johnson, P. Hall, C. Pocock, N. Al Mahdi, John Kenneth Cowell, G. Morgan

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

The t(14;18) translocation is found in the majority follicular lymphomas and some high grade B-cell lymphomas. This is results in deregulation of the BCL-2 gene and appears to play a role in oncogenesis. Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. The mice developed lymphoma bearing the t(14;18) translocation with as few as 5 x 106 cells within 28 days. This was determined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour cells was determined by PCR for the t(14;18) breakpoint region on peripheral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 days the sense, nonsense and untreated cell SCID mice had developed lymphoma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reduction of the BCL-2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.

Original languageEnglish (US)
Pages (from-to)3049-3055
Number of pages7
JournalOncogene
Volume9
Issue number10
StatePublished - Oct 1 1994
Externally publishedYes

Fingerprint

SCID Mice
Antisense Oligonucleotides
B-Cell Lymphoma
Lymphoma
Growth
Genes
Follicular Lymphoma
Human Herpesvirus 4
Oligonucleotides
Non-Hodgkin's Lymphoma
Open Reading Frames
Neoplasms
Carcinogenesis
Cell Count
Cell Line
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Cotter, F. E., Johnson, P., Hall, P., Pocock, C., Al Mahdi, N., Cowell, J. K., & Morgan, G. (1994). Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. Oncogene, 9(10), 3049-3055.

Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. / Cotter, F. E.; Johnson, P.; Hall, P.; Pocock, C.; Al Mahdi, N.; Cowell, John Kenneth; Morgan, G.

In: Oncogene, Vol. 9, No. 10, 01.10.1994, p. 3049-3055.

Research output: Contribution to journalArticle

Cotter, FE, Johnson, P, Hall, P, Pocock, C, Al Mahdi, N, Cowell, JK & Morgan, G 1994, 'Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model', Oncogene, vol. 9, no. 10, pp. 3049-3055.
Cotter FE, Johnson P, Hall P, Pocock C, Al Mahdi N, Cowell JK et al. Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. Oncogene. 1994 Oct 1;9(10):3049-3055.
Cotter, F. E. ; Johnson, P. ; Hall, P. ; Pocock, C. ; Al Mahdi, N. ; Cowell, John Kenneth ; Morgan, G. / Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. In: Oncogene. 1994 ; Vol. 9, No. 10. pp. 3049-3055.
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