COMPARISON OF INFRARED-SPECTRA OF CLL CELLS WITH THEIR EX-VIVO SENSITIVITY (MTT ASSAY) TO CHLORAMBUCIL AND CLADRIBINE

The drug resistance of leukemic cells from 21 patients with chronic ly mphocytic leukemia (CLL) to the alkylating agent chlorambucil (CLB) an d 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 t he infrared spectra of the CLL cells, applying linear discriminant ana lysis (LDA). The 63 spectra (three from each of the 21 samples), obtai ned before drug exposure, were successfully partitioned into drug-sens itive and drug-resistant groups; the LDA-based ex vivo prediction of t he sensitivity to CdA or CLB was 85.7% and 80.3%, respectively. Simila r changes in the composition/structure of DNA were observed between th e spectra of the drug-sensitive and drug-resistant CLL cells for both CdA and CLB. However, CdA-resistant CLL cells could also be differenti ated from CdA-sensitive CLL cells by spectral changes associated with membrane lipids; these differences were much less pronounced between C LB-resistant and CLB-sensitive CLL cells. We demonstrate here for the first time that infrared spectroscopy can be used as a new tool for pr edicting ex vivo drug response (sensitivity/resistance). (C) 1997 Else vier Science Ltd. All rights reserved.