Drug resistance in B-cell chronic lymphocytic leukemia: Predictable by in vitro evaluation with a multiparameter flow cytometric cytotoxicity assay

Yanping Zhong, Antony C. Bakke, Guang Fan, Rita M. Braziel, Ken M. Gatter, Jose F. Leis, Richard T. Maziarz, James Z. Huang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) often demonstrate variable responses to similar treatments. It would be highly desirable to develop a personalized therapeutic strategy for selection of appropriate drugs or regimens based on the drug sensitivity profiles of leukemic cells from individuals. Methods: We applied a multiparameter flow cytometric drug cytotoxicity assay to evaluate drug effects specifically on B-CLL cells from 43 individuals after leukemic cells were incubated in vitro with fludarabine, chlorambucil, cladribine, or prednisolone. Results: We demonstrated that different B-CLL cell populations from 43 individuals showed a marked variability in drug sensitivity. In vitro resistance to fludarabine was greatest in B-CLL cells with deletions of p53, a cytogenetic abnormality that is almost invariably associated with a poor therapeutic response clinically. Conclusions: In vitro drug sensitivity profiles analyzed by a multiparameter flow cytometric cytotoxicity assay may serve as a tool to facilitate individualized selection of appropriate drugs for treatment in B-CLL. Prospective trials will be needed to validate the clinical utility of this flow cytometric cytotoxicity assay.

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalCytometry Part B - Clinical Cytometry
Volume72
Issue number3
DOIs
StatePublished - May 15 2007

Keywords

  • Chronic lymphocytic leukemia
  • Cytotoxicity assay
  • Drug sensitivity
  • Flow cytometry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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