Similarities between the sensitivity to 2-chlorodeoxyadenosine of lymphocytes from CLL patients and bryostatin 1-treated WSU-CLL cells: an infrared spectroscopic study.
Infrared (IR) spectroscopy was used to compare the drug resistance mechanism of cells from chronic lymphocytic leukemia (CLL) patients with that of WSU-CLL cells. Bryostatin 1 (Bryo 1), a macrocyclic lactone and protein kinase C activator, was used to render WSU-CLL cells more susceptible to 2-chlorodeoxyadenosine (2-CdA). The IR spectroscopic analysis revealed some changes in protein and DNA content in Bryo 1-treated WSU-CLL cells, however, the most significant alterations were observed in the membrane lipids, which resemble those found between 2-CdA-sensitive and 2-CdA-resistant cells from CLL patients. In addition, Bryo 1 treatment induced WSU-CLL cells to become CD11c, CD25 and tartrate-resistant acid phosphatase-positive, specific markers for hairy cell leukemia, a disease exquisitely sensitive to 2-CdA. Our results suggest that 2-CdA-sensitive CLL cells have cellular characteristics resembling the hairy cell stage. The similarity between the membrane lipids in 2-CdA-sensitive CLL cells and the Bryo 1-treated WSU-CLL cell line supports the suggestion that membrane lipid alteration might be an important step in the drug resistance mechanism of CLL cells.
Liu
K Z
KZ
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba.
Schultz
C P
CP
Mohammad
R M
RM
Al-Katib
A M
AM
Johnston
J B
JB
Mantsch
H H
HH
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D054713:Bryostatins; D017338:Cladribine / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008214:Lymphocytes / Q000187:drug effects; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D013055:Spectrophotometry, Infrared; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D017338:Cladribine