Drug resistance in B-cell chronic lymphocytic leukemia: predictable by in vitro evaluation with a multiparameter flow cytometric cytotoxicity assay
| Autor: | Guang Fan, Yanping Zhong, Jose F. Leis, Rita M. Braziel, Antony C. Bakke, James Z. Huang, Richard T. Maziarz, Ken M. Gatter |
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| Rok vydání: | 2007 |
| Předmět: |
Drug
Adult Male Histology media_common.quotation_subject Chronic lymphocytic leukemia Antineoplastic Agents Drug resistance Biology Pharmacology Pathology and Forensic Medicine hemic and lymphatic diseases Toxicity Tests medicine Humans Cladribine Cytotoxicity media_common Aged Aged 80 and over Chlorambucil Cell Biology Middle Aged medicine.disease Flow Cytometry Genes p53 Prognosis Leukemia Lymphocytic Chronic B-Cell Fludarabine Leukemia Treatment Outcome Drug Resistance Neoplasm Female Gene Deletion Vidarabine medicine.drug |
| Zdroj: | Cytometry. Part B, Clinical cytometry. 72(3) |
| ISSN: | 1552-4949 |
| Popis: | 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. q 2007 |
| Databáze: | OpenAIRE |
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