High risk of early resistant relapse for leukaemic patients with presence of multidrug resistance associated P-glycoprotein positive cells in complete remission

The immunocytochemical detection of multidrug-resistance (MDR) associated P-glycoprotein (P-170) was longitudinally performed on bone marrow smears from 32 responsive patients with acute leukaemia in the different phases of the disease (at diagnosis, in complete remission, at relapse) by means of APAAP technique and monoclonal antibody C219. The whole group of eight patients with presence of P-170 positive cells while in complete remission rapidly relapsed with a high proportion of blasts showing MDR phenotype; they were resistant to further treatments. Twelve out of 24 subjects without cells with MDR phenotype in complete remission remained in this condition, six had a responsive relapse (without significant expression of P-170 in 5/6 patients) and six a resistant relapse. Four patients of this last group significantly expressed P-170. Our data indicate that the detection of scattered P-170 positive cells during complete remission might identify a subset of leukaemic patients with high risk of early and resistant relapse.     

ASIC proteins regulate smooth muscle cell migration

The purpose of the present study was to investigate Acid Sensing Ion Channel (ASIC) protein expression and importance in cellular migration. We recently demonstrated that Epithelial Na(+)Channel (ENaC) proteins are required for vascular smooth muscle cell (VSMC) migration; however, the role of the closely related ASIC proteins has not been addressed. We used RT-PCR and immunolabeling to determine expression of ASIC1, ASIC2, ASIC3 and ASIC4 in A10 cells. We used small interference RNA to silence individual ASIC expression and determine the importance of ASIC proteins in wound healing and chemotaxis (PDGF-bb)-initiated migration. We found ASIC1, ASIC2, and ASIC3, but not ASIC4, expression in A10 cells. ASIC1, ASIC2, and ASIC3 siRNA molecules significantly suppressed expression of their respective proteins compared to non-targeting siRNA (RISC) transfected controls by 63%, 44%, and 55%, respectively. Wound healing was inhibited by 10, 20, and 26% compared to RISC controls following suppression of ASIC1, ASIC2, and ASIC3, respectively. Chemotactic migration was inhibited by 30% and 45%, respectively, following suppression of ASIC1 and ASIC3. ASIC2 suppression produced a small, but significant, increase in chemotactic migration (4%). Our data indicate that ASIC expression is required for normal migration and may suggest a novel role for ASIC proteins in cellular migration.