SIMILARITIES BETWEEN THE SENSITIVITY TO 2-CHLORODEOXYADENOSINE OF LYMPHOCYTES FROM CLL PATIENTS AND BRYOSTATIN-1-TREATED WSU-CLL CELLS - ANINFRARED SPECTROSCOPIC STUDY

Infrared (LR) spectroscopy was used to compare the drug resistance mec hanism of cells from chronic lymphocytic leukemia (CLL) patients with that of WSU-CLL cells. Bryostatin I (Bryo 1), a macrocyclic lactone an d protein kinase C activator, was used to render WSU-CLL cells more su sceptible to 2-chlorodeoxyadenosine (2-CdA). The IR spectroscopic anal ysis revealed some changes in protein and DNA content in Bryo 1-treate d WSU-CLL cells, however, the most significant alterations were observ ed in the membrane lipids, which resemble those found between 2-CdA-se nsitive 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 l eukemia, a disease exquisitely sensitive to 2-CdA. Our results suggest that 2-CdA-sensitive CLL cells have cellular characteristics resembli ng 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 su pports the suggestion that membrane lipid alteration might be an impor tant step in the drug resistance mechanism of CLL cells. (C) 1998 Else vier Science Ireland Ltd.