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Type: Journal article
Title: OCT-1 function varies with cell lineage but is not influenced by BCR-ABL
Author: Engler, J.
Zannettino, A.
Bailey, C.
Rasko, J.
Hughes, T.
White, D.
Citation: Haematologica: the haematology journal, 2011; 96(2):1-33
Publisher: Fondazione Ferrata Storti
Issue Date: 2011
ISSN: 1592-8721
Statement of
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
RMID: 0020104062
DOI: 10.3324/haematol.2010.033290
Appears in Collections:Medicine publications

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