Lymphoma cells protected from apoptosis by dysregulated bcl-2 continue to bind annexin V in response to B-cell receptor engagement: a cautionary tale

Leuk Res. 2006 Jan;30(1):77-80. doi: 10.1016/j.leukres.2005.05.018. Epub 2005 Aug 1.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism*
  • Antidepressive Agents, Second-Generation / pharmacology
  • Antigens, CD19 / metabolism
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Biological Transport, Active / drug effects
  • Biological Transport, Active / genetics
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 14 / genetics
  • Chromosomes, Human, Pair 14 / metabolism
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 18 / metabolism
  • Fluoxetine / pharmacology
  • Humans
  • Ionophores / pharmacology
  • Lipid Bilayers / metabolism
  • Lymphoma / genetics
  • Lymphoma / metabolism*
  • Lymphoma / pathology
  • Phosphatidylserines / metabolism*
  • Protein Binding / drug effects
  • Protein Binding / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-bcr / metabolism
  • Transfection
  • Transgenes / genetics
  • Translocation, Genetic / genetics

Substances

  • Annexin A5
  • Antidepressive Agents, Second-Generation
  • Antigens, CD19
  • Ionophores
  • Lipid Bilayers
  • Phosphatidylserines
  • Proto-Oncogene Proteins c-bcl-2
  • Fluoxetine
  • BCR protein, human
  • Proto-Oncogene Proteins c-bcr