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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1998-9-10
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pubmed:abstractText |
In vitro studies have provided little consensus on the kinetic abnormality underlying the myeloid expansion of chronic myelogenous leukemia (CML). Transplantation of human CML cells into non-obese diabetic mice with severe immunodeficiency disease (NOD/SCID mice) may therefore be a useful model. A CML cell line (BV173) and peripheral blood cells collected from CML patients in chronic phase (CP), accelerated phase (AP), or blastic phase (BP) were injected into preirradiated NOD/SCID mice. Animals were killed at serial intervals; cell suspensions and/or tissue sections from different organs were studied by immunohistochemistry and/or flow cytometry using antihuman CD45 monoclonal antibodies (MoAbs), and by fluorescence in situ hybridization (FISH) for the BCR-ABL fusion gene. One hour after injection, cells were sequestered in the lungs and liver, but 2 weeks later they were no longer detectable in either site. Similar short-term kinetics were observed using 51Cr-labeled cells. The first signs of engraftment for BV173, AP, and BP cells were detected in the bone marrow (BM) at 4 weeks. At 8 weeks the median percentages of human cells in murine marrow were 4% (range, 1 to 9) for CP, 11% (range, 5 to 36) for AP, 38.5% (range, 18 to 79) for BP, and 54% (range, 31 to 69) for BV173. CP cells progressively infiltrated BM (21%) and spleen (6%) by 18 to 20 weeks; no animals injected with the cell line or BP cells survived beyond 12 weeks. The rate of increase in human cell numbers was higher for BP (7.3%/week) as compared with CP (0.9%/week) and AP (0. 5%/week). FISH analysis with BCR and ABL probes showed that some of the human cells engrafting after injection of CP cells lacked a BCR-ABL gene and were presumably normal. We conclude that CML cells proliferate in NOD/SCID mice with kinetics that recapitulate the phase of the donor's disease, thus providing an in vivo model of CML biology.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1998 by The American Society of Hematology.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1390-6
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9694728-Animals,
pubmed-meshheading:9694728-Blast Crisis,
pubmed-meshheading:9694728-Bone Marrow,
pubmed-meshheading:9694728-DNA, Neoplasm,
pubmed-meshheading:9694728-Disease Progression,
pubmed-meshheading:9694728-Fusion Proteins, bcr-abl,
pubmed-meshheading:9694728-Graft Survival,
pubmed-meshheading:9694728-Humans,
pubmed-meshheading:9694728-In Situ Hybridization,
pubmed-meshheading:9694728-Kinetics,
pubmed-meshheading:9694728-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:9694728-Leukemia, Myeloid, Accelerated Phase,
pubmed-meshheading:9694728-Leukemia, Myeloid, Chronic-Phase,
pubmed-meshheading:9694728-Liver,
pubmed-meshheading:9694728-Lung,
pubmed-meshheading:9694728-Mice,
pubmed-meshheading:9694728-Mice, Inbred NOD,
pubmed-meshheading:9694728-Mice, SCID,
pubmed-meshheading:9694728-Neoplasm Transplantation,
pubmed-meshheading:9694728-Neoplastic Cells, Circulating,
pubmed-meshheading:9694728-Neoplastic Stem Cells,
pubmed-meshheading:9694728-Specific Pathogen-Free Organisms,
pubmed-meshheading:9694728-Tissue Distribution,
pubmed-meshheading:9694728-Transplantation, Heterologous,
pubmed-meshheading:9694728-Tumor Markers, Biological
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pubmed:year |
1998
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pubmed:articleTitle |
The kinetics and extent of engraftment of chronic myelogenous leukemia cells in non-obese diabetic/severe combined immunodeficiency mice reflect the phase of the donor's disease: an in vivo model of chronic myelogenous leukemia biology.
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pubmed:affiliation |
Department of Haematology, Imperial College School of Medicine at Hammersmith Hospital, London, UK. f.dazzi@rpms.ac.uk
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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