DIFFERENCES IN RHODAMINE-123 EFFLUX IN B-TYPE CHRONIC LYMPHOCYTIC-LEUKEMIA SUGGEST POSSIBLE GENDER AND STAGE VARIATIONS IN DRUG-RESISTANCE GENE ACTIVITY

Peripheral blood samples from 61 patients (36 male, 25 female) with al l stages of B-type chronic lymphocytic leukemia (CLL) were studied for MDR1 phenotype using monoclonal antibodies and rhodamine-123 dye excl usion, a functional assay of MDR1 expression. The duration of the dise ase varied from 1 month to 22 years at the time of initial study. Over all, 74% of the patients were positive for rhodamine-123 exclusion, Wh en analyzed by gender, significantly more men than women were positive (89% versus 48%, p < 0.001), There were more positive men than women for every stage of the disease. Female patients were found to be eithe r MDR1 phenotype positive or negative at any stage of the disease. In contrast, all male patients with early (stages 0-II) disease were MDR1 phenotype positive. One early-stage (stage II) male patient converted from rhodamine-efflux positive to rhodamine-efflux negative as he pro gressed from stage-II to stage-IV disease; We suggest that some of the differences in disease biology of male versus female CLL patients (wo men having a more benign course) may be due to gender-dependent differ ences in drug-resistance gene activity, including MDR1. Our results al so emphasize the need to take into account gender in evaluating the cl inical course of patients with CLL.