title: Flow cytometric chemosensitivity assay using JC‑1, a sensor of mitochondrial transmembrane potential, in acute leukemia.
abstract: OBJECTIVE
  The purpose of the study is to establish a simple and relatively inexpensive flow cytometric chemosensitivity assay (FCCA) for leukemia to distinguish leukemic blasts from normal leukocytes in clinical samples.
  
  
  METHODS
  We first examined whether the FCCA with the mitochondrial membrane depolarization sensor, 5, 50, 6, 60-tetrachloro-1, 10, 3, 30 tetraethyl benzimidazolo carbocyanine iodide (JC-1), could detect drug-induced apoptosis as the conventional FCCA by annexin V/7-AAD detection did and whether it was applicable in the clinical samples. Second, we compared the results of the FCCA for prednisolone (PSL) with clinical PSL response in 18 acute lymphoblastic leukemia (ALL) patients to evaluate the reliability of the JC-1 FCCA. Finally, we performed the JC-1 FCCA for bortezomib (Bor) in 25 ALL or 11 acute myeloid leukemia (AML) samples as the example of the clinical application of the FCCA.
  
  
  RESULTS
  In ALL cells, the results of the JC-1 FCCA for nine anticancer drugs were well correlated with those of the conventional FCCA using anti-annexin V antibody (P < 0.001). In the clinical samples from 18 children with ALL, the results of the JC-1 FCCA for PSL were significantly correlated with the clinical PSL response (P = 0.005). In ALL samples, the sensitivity for Bor was found to be significantly correlated with the sensitivity for PSL (P = 0.005). In AML samples, the Bor sensitivity was strongly correlated with the cytarabine sensitivity (P = 0.0003).
  
  
  CONCLUSIONS
  This study showed the reliability of a relatively simple and the FCCA using JC-1, and the possibility for the further clinical application.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yokosuka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Goto
authors.forename: Hisaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.forename: Masanobu
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Reo
authors.initials: R
authors.lastname: Tanoshima
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kato
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Yanagimachi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kajiwara
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yokota
mesh_terms: D000293:Adolescent; D017304:Annexin A5 / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D002232:Carbocyanines; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry / Q000379:methods*; D005456:Fluorescent Dyes; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine