Human Philadelphia chromosome-positive chronic myeloid leukemia: a potential model for antisense therapy.
We have developed an in vivo model of human chronic myeloid leukemia (CML). A peripheral blood (PB) sample of Philadelphia (Ph) chromosome-positive CML cells in lymphoid blast crisis was transplanted intravenously (IV) into sublethally irradiated severe combined immunodeficient (SCID) mice, and this resulted in engraftment with systemic proliferation. Growth of leukemia was monitored by PB cell morphology and by flow cytometric analysis of murine PB cells labelled with an anti-human leukocyte antigen (HLA) monoclonal antibody. Human cells were first detected in the PB at 4 weeks and comprised a mean of 57% of the total nucleated cells in the PB of these mice by 15 weeks. The Ph chromosome was retained and the population has been successfully passaged. BCR/ABL fusion gene expression was detected in a subsequent passage. Experiments are underway to use this in vivo model to assess the antileukemic activity of BCR/ABL antisense oligonucleotides.
Section of Medicine, Institute of Cancer Research, Sutton, Surrey, England.
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De Lord
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Clutterbuck
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Powles
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Min
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Titley
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Millar
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D001402:B-Lymphocytes / Q000473:pathology; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006680:HLA Antigens / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics; D051562:Proto-Oncogene Proteins c-bcr; D013601:T-Lymphocytes / Q000473:pathology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr