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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9-10
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pubmed:dateCreated |
1999-4-15
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pubmed:abstractText |
Bryostatin-1 belongs to the family of macrocyclic lactones isolated from the marine bryozoan Bugula neritina and is a potent activator of protein kinase C (PKC). Bryostatin has been demonstrated to possess both in vivo and in vitro anti-leukaemic potential. In samples derived from chronic myeloid leukaemia (CML) patients, it has been demonstrated that bryostatin-1 induces a macrophage differentiation, suppresses colony growth in vitro and promotes cytokine secretion from accessory cells. We investigated the effect of bryostatin-1 treatment on colony-forming unit-granulocyte macrophage (CFU-GM) capacity in the presence of accessory cells, using mononuclear cells, as well as in the absence of accessory cells using purified CD34-positive cells. Cells were obtained from 14 CML patients as well as from nine controls. Moreover, CD34-positive cells derived from CML samples and controls were analysed for stem cell frequency and ability using the long-term culture initiating cell (LTCIC) assay at limiting dilution. Individual colonies derived from both the CFU-GM and LTCIC assays were analysed for the presence of the bcr-abl gene with fluorescence in situ hybridization (FISH) to evaluate inhibition of malignant colony growth. The results show that at the CFU-GM level bryostatin-1 treatment resulted in only a 1.4-fold higher reduction of CML colony growth as compared to the control samples, both in the presence and in the absence of accessory cells. However, at the LTCIC level a sixfold higher reduction of CML growth was observed as compared to the control samples. Analysis of the LTCICs at limiting dilution indicates that this purging effect is caused by a decrease in output per malignant LTCIC combined with an increase in the normal stem cell frequency. It is concluded that bryostatin-1 selectively inhibits CML growth at the LTCIC level and should be explored as a purging modality in CML.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-1375394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-1498072,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-1656993,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-1712111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-2033960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-2265553,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-2310830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-2333304,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-2386956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-2989692,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-2996535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-300256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-3125421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-3174627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-3783162,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-6574315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-7575530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-7640233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-7641182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-7807010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-7837820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8043861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8118022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8160269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8161775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8165725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8230254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8379003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8477194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8499629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8605966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8947584,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-8950237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-9009097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-9440723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10188883-9533528
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
79
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1406-12
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10188883-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:10188883-Bryostatins,
pubmed-meshheading:10188883-Enzyme Activation,
pubmed-meshheading:10188883-Fusion Proteins, bcr-abl,
pubmed-meshheading:10188883-Granulocytes,
pubmed-meshheading:10188883-Hematopoietic Stem Cells,
pubmed-meshheading:10188883-Humans,
pubmed-meshheading:10188883-In Situ Hybridization, Fluorescence,
pubmed-meshheading:10188883-Lactones,
pubmed-meshheading:10188883-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:10188883-Macrolides,
pubmed-meshheading:10188883-Macrophages,
pubmed-meshheading:10188883-Tumor Stem Cell Assay
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pubmed:year |
1999
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pubmed:articleTitle |
Effects of bryostatin-1 on chronic myeloid leukaemia-derived haematopoietic progenitors.
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pubmed:affiliation |
Department of Haematology, Free University Hospital, Amsterdam.
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pubmed:publicationType |
Journal Article
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