Bcl-2 protein expression and p53 gene mutation in chronic lymphocytic leukemia: Correlation with in vitro sensitivity to chlorambucil and purine analogs

Fortunato Morabito, Monica Filangeri, Ida Callea, Giuseppina Sculli, Vincenzo Callea, Nicola S. Fracchiolla, Antonino Neri, Maura Brugiatelli

Research output: Contribution to journalArticle

Abstract

Background and Objective. Bcl-2 oncogenic protein expression plays a major role in blocking the apoptotic mechanism. p53 gene mutations have also been suggested to account for the chlorambucil resistance in CLL. Thus we studied the relationship between bcl-2 protein expression, p53 gene mutations and in vitro drug sensitivity in CLL. Methods. Fifty-three samples from uncreated CLL patients in early disease stages were tested in vitro for chemosensitivity to chlorambucil (CLB), fludarabine (FAMP) and 2- chlorodeoxyadenosine (2-CDA) using the MTT assay. Intracellular bcl-2 protein expression was evaluated by flow cytometry analysis. p53 gene mutations were detected by using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. Results. The median LD50 values were 1.55 μM, 4.41 μM and 58.2 μM for 2-CDA, FAMP and CLB, respectively. About 23%, 41% and 11% of samples were defined as being sensitive to FAMP, 2-CDA and CLB, respectively, when samples were clustered for LD50 threshold values corresponding to the plasmatic levels of the drug. No statistically significant difference in bcl-2 protein expression was noted between sensitive and resistant samples for each drug. A p53 gene mutation was detected in 4 of the 30 cases studied and all of them were among samples resistant to CLB. Interpretation and Conclusions. Bcl-2 expression is not an indicator of in vitro response to drugs in CLL; similarly, although the four cases showing a p53 gene mutation were associated with CLB resistance, drug resistant samples were also observed in the group of patients showing wild type p53, suggesting multiple mechanisms of drug resistance in CLL.

Original languageEnglish
Pages (from-to)16-20
Number of pages5
JournalHaematologica
Volume82
Issue number1
Publication statusPublished - Jan 1997

Fingerprint

Chlorambucil
p53 Genes
B-Cell Chronic Lymphocytic Leukemia
Cladribine
Mutation
Proteins
Lethal Dose 50
Pharmaceutical Preparations
Multiple Drug Resistance
Drug Resistance
In Vitro Techniques
purine
Flow Cytometry
Polymerase Chain Reaction

Keywords

  • Bcl-2
  • Chemosensitivity
  • CLL
  • MTT assay
  • p53

ASJC Scopus subject areas

  • Hematology

Cite this

Bcl-2 protein expression and p53 gene mutation in chronic lymphocytic leukemia : Correlation with in vitro sensitivity to chlorambucil and purine analogs. / Morabito, Fortunato; Filangeri, Monica; Callea, Ida; Sculli, Giuseppina; Callea, Vincenzo; Fracchiolla, Nicola S.; Neri, Antonino; Brugiatelli, Maura.

In: Haematologica, Vol. 82, No. 1, 01.1997, p. 16-20.

Research output: Contribution to journalArticle

Morabito, Fortunato ; Filangeri, Monica ; Callea, Ida ; Sculli, Giuseppina ; Callea, Vincenzo ; Fracchiolla, Nicola S. ; Neri, Antonino ; Brugiatelli, Maura. / Bcl-2 protein expression and p53 gene mutation in chronic lymphocytic leukemia : Correlation with in vitro sensitivity to chlorambucil and purine analogs. In: Haematologica. 1997 ; Vol. 82, No. 1. pp. 16-20.
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