Apoptosis (programmed cell death) and the evaluation of chemosensitivity in chronic lymphocytic leukemia and lymphoma

Oskar S. Frankfurt, John Byrnes, Daniel Seckinger, Everett V. Sugarbaker

Research output: Contribution to journalArticle

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Abstract

Chronic lymphocytic leukemia and lymphoma cells were treated with antitumor drugs in vitro and analyzed by flow cytometry to measure the number of apoptotic (AP) cells and DNA damage in the cells that escaped apoptotic death. AP cells were identified by a high sensitivity of DNA to thermal denaturation, which induced binding of antibody to single-stranded DNA, and by decreased stainability of cells with the intercalating DNA dye propidium iodide. The appearance of AP cells was prevented by Zn++ and inhibited by phorbol ester. AP cells were induced by alkylating agents, antimetabolites, and anthracyclines. A linear relationship between L-phenylalanine mustard dose and the number of AP cells was observed. A synergistic interaction between drugs was detected by an increased number of AP cells and by the intensity of DNA damage in non-apoptotic cells. A most interesting example of synergism was the combination of alkylating agents with fludarabine. Linearity of dose-response curves, and the capability to detect drug synergism and to evaluate variable response of cells from different patients to single agents and combinations suggest that flow cytometry of apoptosis will provide a basis for chemosensitivity tests in leukemia and lymphoma.

Original languageEnglish
Pages (from-to)37-42
Number of pages6
JournalOncology Research
Volume5
Issue number1
StatePublished - Dec 1 1993

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B-Cell Chronic Lymphocytic Leukemia
Cell Death
Apoptosis
Cell Count
Alkylating Agents
DNA Damage
Flow Cytometry
Drug Synergism
Antimetabolites
Melphalan
Propidium
Single-Stranded DNA
Anthracyclines
DNA
Phorbol Esters
Phenylalanine
Drug Interactions
Antineoplastic Agents
Lymphoma
Leukemia

ASJC Scopus subject areas

  • Cancer Research

Cite this

Apoptosis (programmed cell death) and the evaluation of chemosensitivity in chronic lymphocytic leukemia and lymphoma. / Frankfurt, Oskar S.; Byrnes, John; Seckinger, Daniel; Sugarbaker, Everett V.

In: Oncology Research, Vol. 5, No. 1, 01.12.1993, p. 37-42.

Research output: Contribution to journalArticle

Frankfurt, Oskar S. ; Byrnes, John ; Seckinger, Daniel ; Sugarbaker, Everett V. / Apoptosis (programmed cell death) and the evaluation of chemosensitivity in chronic lymphocytic leukemia and lymphoma. In: Oncology Research. 1993 ; Vol. 5, No. 1. pp. 37-42.
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