17p Deletion is associated with resistance of B-cell chronic lymphocytic leukemia cells to in vitro fludarabine-induced apoptosis

Leuk Lymphoma. 2007 Feb;48(2):311-20. doi: 10.1080/10428190601059829.

Abstract

We explored the relationship between the cytogenetic/biologic characteristics of B-chronic lymphocytic leukemia (B-CLL) cells and their tendency to undergo spontaneous or fludarabine-induced apoptosis in vitro. B cells from 36 B-CLL patients were incubated with or without fludarabine for 48 h. Apoptosis was determined by two assays: annexin V staining and DNA staining. Fluorescence in situ hybridization was used for detection of trisomy 12, 11q deletion, and 17p deletion. Bcl-2 and CD38 expressions were determined by flow cytometry. Five patients had 17p deletion, 6 had trisomy 12, and another 6 had 11q deletion. B-CLL cells with 17p deletion had significant resistance to apoptosis induced by fludarabine and a slight spontaneous resistance to apoptosis. Bcl-2 and CD38 were not associated with in vitro spontaneous and fludarabine-induced apoptosis. In conclusion, 17p deletion, which causes loss of p53 gene, is associated with resistance to fludarabine-induced apoptosis in vitro. New treatment modalities should be tried in B-CLL patients with 17p deletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • Female
  • Flow Cytometry
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacology

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • DNA (Cytosine-5-)-Methyltransferases
  • ADP-ribosyl Cyclase 1
  • Vidarabine
  • fludarabine