Transformation of hematopoietic cells by the p210bcr/abl tyrosine kinase appears to require the expression of a functional MYC protein, suggesting that simultaneous targeting of BCR-ABL and c-myc might be a rational strategy for attempting treatment of Phil-adelphia leukemia. To test this hypothesis, severe combined immunodeficiency mice injected with Philadelphia leukemic cells were treated systemically with equal doses of bcr-abl or c-myc antisense oligodeoxynucleotides (ODNs) or with both ODNs in combination. Compared with the mice treated with individual agents, the disease process was much slower in the group treated with both ODNs, as revealed by flow cytometry, clonogenic assay, and reverse transcriptase-polymerase chain reaction analysis to detect leukemic cells in mouse tissue cell suspensions, and by enumeration of liver metastases. The retardation of the disease process was positively correlated with a markedly increased survival of leukemic mice treated with both ODNs. These data demonstrate the therapeutic potential of targeting multiple cooperating oncogenes.

Leukemia treatment in severe combined immunodeficiency mice by antisense oligodeoxynucleotides targeting cooperating oncogenes / Skorski, T; Nieborowska Skorska, M; Campbell, K; Iozzo, Rv; Zon, G; Darzynkiewicz, Z; Calabretta, Bruno. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - STAMPA. - 182:(1995), pp. 1645-1653.

Leukemia treatment in severe combined immunodeficiency mice by antisense oligodeoxynucleotides targeting cooperating oncogenes.

CALABRETTA, Bruno
1995

Abstract

Transformation of hematopoietic cells by the p210bcr/abl tyrosine kinase appears to require the expression of a functional MYC protein, suggesting that simultaneous targeting of BCR-ABL and c-myc might be a rational strategy for attempting treatment of Phil-adelphia leukemia. To test this hypothesis, severe combined immunodeficiency mice injected with Philadelphia leukemic cells were treated systemically with equal doses of bcr-abl or c-myc antisense oligodeoxynucleotides (ODNs) or with both ODNs in combination. Compared with the mice treated with individual agents, the disease process was much slower in the group treated with both ODNs, as revealed by flow cytometry, clonogenic assay, and reverse transcriptase-polymerase chain reaction analysis to detect leukemic cells in mouse tissue cell suspensions, and by enumeration of liver metastases. The retardation of the disease process was positively correlated with a markedly increased survival of leukemic mice treated with both ODNs. These data demonstrate the therapeutic potential of targeting multiple cooperating oncogenes.
1995
182
1645
1653
Leukemia treatment in severe combined immunodeficiency mice by antisense oligodeoxynucleotides targeting cooperating oncogenes / Skorski, T; Nieborowska Skorska, M; Campbell, K; Iozzo, Rv; Zon, G; Darzynkiewicz, Z; Calabretta, Bruno. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - STAMPA. - 182:(1995), pp. 1645-1653.
Skorski, T; Nieborowska Skorska, M; Campbell, K; Iozzo, Rv; Zon, G; Darzynkiewicz, Z; Calabretta, Bruno
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/812302
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