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The Gene Expressions of hOCT1 and ABCB1 Change During the Course of CML in Relation to Imatinib Therapy

Authors :
Jitka Koblihova
Zdenek Racil
Daniela Zackova
Jiri Mayer
Katerina Machova Polakova
Filip Rázga
Marek Trneny
Zuzana Ondrackova
Vaclava Polivkova
Hana Klamova
Petr Cetkovsky
Source :
Blood. 118:2495-2495
Publication Year :
2011
Publisher :
American Society of Hematology, 2011.

Abstract

Abstract 2495 Background. The intracellular concentration of imatinib (IM) in patients with chronic myeloid leukemia (CML) is supposed to be influenced by the expression of its main cellular transporters, hOCT1 (influx) and ABCB1 (efflux). The assessment of the genes expression may be potentially important in clinical practice to effectively manage the therapy. Our recent results showed the necessity to cautiously interpret results from gene expression measurements of both transporters as their detected mRNA levels are affected by the proportion of different cell types in the sample analyzed (Racil et al. 2010 Am J Hem 85:525, Racil et al. 2011 Leuk & Lymph 52:331). Aims. In this report, we aimed to comprehensively assess differences in the expression of hOCT1 and ABCB1 in total leukocytes of peripheral blood (PB) in relation to the blood cell lineage in CML patients with different responses to IM. Methods. Kruskall Wallis's and Dunn's multiple comparison tests were applied to calculate differences in transcript levels of hOCT1 and ABCB1 in patients at diagnosis (Dg=43), in major molecular response (MMR=27), complete molecular response (BCR-ABL log 4.5 reduction; CMR4.5 =15), therapy failure (TF=13), accelerated phase (AP=12) and in 75 healthy controls. CMR4.5 is defined here as either a detectable disease ≤0.0032% BCR-ABLIS or as undetectable by nested PCR. TF is defined as non CCgR achievement. Additionally, we used the Spearman's correlation test to investigate relationship between expressions and percentage of immature cells and neutrophils in patients with non-physiological blood count (Dg and AP). In patients with normal blood count (CMR4.5, MMR, TF), we calculated correlation with BCR-ABL transcript level. Finally, we performed in vitro experiments with BCR-ABL negative (SKM-1, MOLM-13) and positive cell lines (K562, MOLM-7) treated with IM to study its effect on ABCB1 expression. Results. We found a significantly lower expression of hOCT1 and ABCB1 at Dg (P Disclosures: Machova Polakova: Novartis: travel grant. Ondrackova:BMS: travel grant.

Details

ISSN :
15280020 and 00064971
Volume :
118
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi...........1ad69edc5331769004e0f3741845f501
Full Text :
https://doi.org/10.1182/blood.v118.21.2495.2495