OCT-1 Function Varies with Cell Lineage but is Not Influenced by BCR-ABL

Overview

Journal Haematologica

Specialty Hematology

Date 2010 Oct 26

PMID 20971815

Citations 8

Authors

Jane R Engler

Andrew C W Zannettino

Charles G Bailey

John E J Rasko

Timothy P Hughes

Deborah L White

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Design And Methods: 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.

Results: 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).

Conclusions: 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.

Citing Articles

OCT-1 Expression in Patients with Chronic Myeloid Leukemia: A Comparative Analysis with Respect to Response to Imatinib Treatment.

Bozkurt Bulakci B, Aday A, Gurtekin B, Yavuz A, Ozturk S, Cefle K Indian J Hematol Blood Transfus. 2022; 38(4):668-674.

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Imatinib Affects the Expression of SLC22A1 in a Non-Linear Concentration-Dependent Manner Within 24 Hours.

Sreenivasan Tantuan S, Viljoen C Med Sci Monit Basic Res. 2018; 24:59-62.

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Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells.

Wang J, Lu L, Kok C, Saunders V, Goyne J, Dang P Haematologica. 2017; 102(5):843-853.

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Gene expression patterns as predictive biomarkers in hematology-oncology: principal hurdles on the road to the clinic.

Razga F, Nemethova V Haematologica. 2017; 102(1):e31-e32.

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Significance of OCT1 Expression in Acute Myeloid Leukemia.

Stefanko E, Rybka J, Jazwiec B, Haus O, Stapor S, Kuliczkowski K Pathol Oncol Res. 2016; 23(3):665-671.

PMID: 28025785 DOI: 10.1007/s12253-016-0161-7.

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