Expression of CD10 by B-chronic lymphocytic leukemia cells undergoing apoptosis in vivo and in vitro

Haematologica. 2003 Aug;88(8):864-73.

Abstract

Background and objectives: B-cell chronic lymphocytic leukemia (B-CLL) is an accumulating disease of slowly proliferating cells. CD10 is not normally expressed on the surface of B-CLL cells. The aim of this study was to ascertain whether B-CLL cells, induced into apoptosis, expressed surface CD10, since a correlation between apoptosis and CD10 expression has been demonstrated.

Design and methods: Peripheral blood cells from 31 untreated B-CLL patients were induced into apoptosis by etoposide, fludarabine or Ga(mu)-Ab treatment and tested for CD10 expression by flow cytometry. Normal CD5+ B cells were also induced into apoptosis and tested for CD10 expression.

Results: CD10 positive cells were absent in B-CLL cell suspensions, but were detected following in vitro culture, and their appearance paralleled that of apoptotic cells. Treatment with etoposide, fludarabine or Ga(mu)-Ab enhanced both apoptosis and CD10 expression. Inhibition of apoptosis by VAD-fmk or Ga(delta)-Ab prevented CD10 expression. Cell separation tests following induction of apoptosis demonstrated that CD10+ cells were apoptotic. CD10+ cells were observed in the peripheral blood of two patients within a few hours following fludarabine infusion. In another patient, who failed to respond, no CD10+ cells were seen. Expression of CD10 was observed also in normal CD5+ B cells when these were induced into apoptosis.

Interpretation and conclusions: This study demonstrates that B-CLL cells, as well as normal CD5+ B cells, become CD10+ following apoptosis induction in vitro. Some of the data obtained also suggest a use for CD10 to monitor apoptosis of B-CLL in a clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / immunology
  • ADP-ribosyl Cyclase / metabolism
  • ADP-ribosyl Cyclase 1
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Antibodies / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Apoptosis / physiology*
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Etoposide / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Immunoglobulin A / pharmacology
  • Immunoglobulin D / pharmacology
  • Immunoglobulin M / pharmacology
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Membrane Glycoproteins
  • Neprilysin / biosynthesis*
  • Palatine Tonsil
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacology

Substances

  • Amino Acid Chloromethyl Ketones
  • Antibodies
  • Antibodies, Monoclonal
  • Antigens, CD
  • Immunoglobulin A
  • Immunoglobulin D
  • Immunoglobulin M
  • Membrane Glycoproteins
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Etoposide
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • Neprilysin
  • Vidarabine
  • fludarabine