title: Comparison of infrared spectra of CLL cells with their ex vivo sensitivity (MTT assay) to chlorambucil and cladribine.
abstract: The drug resistance of leukemic cells from 21 patients with chronic lymphocytic leukemia (CLL) to the alkylating agent chlorambucil (CLB) and the nucleoside analog cladribine or 2-chlorodeoxyadenosine (CdA) was investigated by infrared spectroscopy. Drug sensitivities, determined in vitro with the tetrazolium dye (MTT) assay, were correlated with the infrared spectra of the CLL cells, applying linear discriminant analysis (LDA). The 63 spectra (three from each of the 21 samples), obtained before drug exposure, were successfully partitioned into drug-sensitive and drug-resistant groups; the LDA-based ex vivo prediction of the sensitivity to CdA or CLB was 85.7% and 80.3%, respectively. Similar changes in the composition/structure of DNA were observed between the spectra of the drug-sensitive and drug-resistant CLL cells for both CdA and CLB. However, CdA-resistant CLL cells could also be differentiated from CdA-sensitive CLL cells by spectral changes associated with membrane lipids; these differences were much less pronounced between CLB-resistant and CLB-sensitive CLL cells. We demonstrate here for the first time that infrared spectroscopy can be used as a new tool for predicting ex vivo drug response (sensitivity/resistance).
authors.affiliation: Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba.
authors.forename: K Z
authors.initials: KZ
authors.lastname: Liu
authors.forename: C P
authors.initials: CP
authors.lastname: Schultz
authors.forename: J B
authors.initials: JB
authors.lastname: Johnston
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: H H
authors.initials: HH
authors.lastname: Mantsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D017338:Cladribine / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000097:blood; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D017550:Spectroscopy, Fourier Transform Infrared; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D008055:Lipids; D009363:Neoplasm Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D002699:Chlorambucil; D017338:Cladribine; C022616:thiazolyl blue