CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age

Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein (MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients >or=60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p < 0.05, p < 0.001, p < 0.001 and p < 0.001). Higher BCRP mRNA was associated with secondary AML (p < 0.05). MDR1 and BCRP mRNA were highly significantly associated (p < 0.001), as were MRP1 and LRP mRNA (p < 0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p = 0.03), thereby identifying a clinically resistant subgroup of elderly AML patients.

Intelligence and the psychological refractory period: A lateralized readiness potential study

The psychological refractory period (PRP) refers to a delay of response times (RT) to the second of two stimuli when these stimuli are presented in rapid succession. If this limitation of rapidly processing the second stimulus contributes to the well-known differences in speed of information processing between individuals with higher and lower mental ability, individuals with lower mental ability should exhibit a more pronounced PRP effect than individuals with higher mental ability. Previous studies on this question, however, yielded inconsistent results. In the present study, we assessed mental ability-related differences in the PRP by measuring lateralized readiness potentials (LRPs) to separate premotor and motor aspects of speed of information processing in 95 individuals with higher and 95 individuals with lower mental ability. Although individuals with higher mental ability processed information faster than individuals with lower mental ability as indicated by shorter RTs and shorter premotor LRP latencies, the PRP effect was equally pronounced in both groups. These findings suggest that the processes underlying the PRP effect do not contribute to mental ability-related differences in speed of information processing. Rather, these differences seem to occur at an earlier stage of information processing such as stimulus encoding, stimulus analysis, or stimulus evaluation.