title: Drug resistance in B-cell chronic lymphocytic leukemia: predictable by in vitro evaluation with a multiparameter flow cytometric cytotoxicity assay.
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.
authors.affiliation: Department of Pathology, Oregon Heath and Science University, Portland, Oregon 97201-3098, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhong
authors.forename: Antony C
authors.initials: AC
authors.lastname: Bakke
authors.forename: Guang
authors.initials: G
authors.lastname: Fan
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Ken M
authors.initials: KM
authors.lastname: Gatter
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: James Z
authors.initials: JZ
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018675:Toxicity Tests / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine