Abstract
Translocation of phosphatidylserine (PS) from the inner to outer leaflet of the surface membrane lipid bilayer, a characteristic early event of cells entering the apoptotic program, is routinely assessed by the Ca(2+)-dependent binding of Annexin V (AV). Here, we show that lymphoma cells protected from apoptosis by expression of a bcl-2 transgene or by virtue of the t(14;18)(q32;q21) translocation continue to register enhanced AV binding in response to BCR crosslinking. Induced AV binding appeared BCR-selective in that it did not proceed in Bcl-2(high) cells in response to calcium ionophore or the antidepressant fluoxetine, each of which activate the full apoptotic program in Bcl-2(low) equivalents. AV-positive cells did increase on crosslinking the BCR co-receptor CD19, despite it being a completely non-apoptotic signal. These findings advise caution when interpreting studies where Annexin V binding is used as a sole, or major, indicator of apoptotic death among lymphoma B cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Annexin A5 / metabolism*
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Antidepressive Agents, Second-Generation / pharmacology
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Antigens, CD19 / metabolism
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Apoptosis* / drug effects
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Apoptosis* / genetics
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B-Lymphocytes / metabolism*
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B-Lymphocytes / pathology
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Biological Transport, Active / drug effects
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Biological Transport, Active / genetics
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Cell Line, Tumor
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Chromosomes, Human, Pair 14 / genetics
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Chromosomes, Human, Pair 14 / metabolism
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Chromosomes, Human, Pair 18 / genetics
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Chromosomes, Human, Pair 18 / metabolism
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Fluoxetine / pharmacology
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Humans
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Ionophores / pharmacology
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Lipid Bilayers / metabolism
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Lymphoma / genetics
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Lymphoma / metabolism*
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Lymphoma / pathology
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Phosphatidylserines / metabolism*
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Protein Binding / drug effects
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Protein Binding / genetics
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Proto-Oncogene Proteins c-bcr / metabolism
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Transfection
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Transgenes / genetics
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Translocation, Genetic / genetics
Substances
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Annexin A5
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Antidepressive Agents, Second-Generation
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Antigens, CD19
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Ionophores
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Lipid Bilayers
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Phosphatidylserines
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Proto-Oncogene Proteins c-bcl-2
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Fluoxetine
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BCR protein, human
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Proto-Oncogene Proteins c-bcr