Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||OCT-1 function varies with cell lineage but is not influenced by BCR-ABL|
|Citation:||Haematologica: the haematology journal, 2011; 96(2):1-33|
|Publisher:||Fondazione Ferrata Storti|
|Jane R. Engler, Andrew C.W. Zannettino, Charles G. Bailey, John E.J. Rasko, Timothy P. Hughes and Deborah L. White|
|Abstract:||<h4>Background</h4>Despite the excellent responses to imatinib therapy observed in patients with chronic phase chronic myeloid leukemia, approximately 25% of patients display primary resistance or suboptimal response. The OCT-1 activity in mononuclear cells reflects the efficiency of active influx of imatinib. OCT-1 activity in mononuclear cells is highly variable between patients and significantly correlates with a patient's molecular response to imatinib treatment and overall survival. The present study examined whether cell lineage and BCR-ABL expression influenced OCT-1 activity.<h4>Design and methods</h4>The OCT-1 activity and OCT-1 mRNA expression was assessed in pure populations of neutrophils, monocytes and lymphocytes recovered from chronic myeloid leukemia patients at diagnosis, in cytogenetic remission and normal individuals. The role of BCR-ABL on OCT-1 activity and differentiation was examined in a cell line model of ectopic BCR-ABL expression.<h4>Results</h4>The OCT-1 activity and OCT-1 mRNA expression was highest in the neutrophil population and lowest in lymphocytes (P<0.05). This was observed for patients at diagnosis, in cytogenetic remission and normal individuals. Interestingly, neutrophil OCT-1 activity was not significantly different between patients at diagnosis, in remission and normal donors. This was also observed for monocytes and lymphocytes. Furthermore, OCT-1 activity in mononuclear cells was significantly correlated with the OCT-1 activity in neutrophils (P=0.001). In a cell line model in which BCR-ABL was ectopically expressed, we found no evidence that BCR-ABL directly affected OCT-1 expression and function. However, BCR-ABL stimulated granulocyte differentiation which, in turn, led to significantly increased OCT-1 activity (P=0.024).<h4>Conclusions</h4>These studies suggest that the predictive OCT-1 activity in patient mononuclear cells is strongly related to cell lineage, particularly the presence of neutrophils in the peripheral blood. Furthermore, BCR-ABL expression is unlikely to directly influence OCT-1 activity but may have an indirect role by enhancing granulocyte differentiation.|
|Keywords:||chronic myeloid leukemia; OCT-1; OCT-1 activity; BCR-ABL; imatinib.|
|Rights:||Copyright © 2011 by Ferrata Storti Foundation|
|Appears in Collections:||Medicine publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.