In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1097-1097
Abstract:
Introduction: Treatment of chronic myeloid leukemia (CML) with the BCR/ABL-inhibitor imatinib led to a tremendous progress of over-all survival. However therapy resistance in a significant proportion of patients remains a severe clinical problem. Aside mutations of the BCR/ABL gene, regulation of cellular transporters or downstream factors may contribute to non-response. We aimed to investigate micro-RNA expression profiles in peripheral leukocytes of 21 newly diagnosed CML patients without BCR/ABL-mutations in order to identify biomarkers to treatment-response of imatinib. Methods: Ten responders (molecular remission) and 11 non-responders were included. Expression of 667 microRNAs was analyzed using a TaqMan Low-Density Array system. Relative fold change of microRNAs between groups was calculated according to the 2^-ΔΔCt method. MicroRNAs with a fold change & gt;2 and a P-value & lt;0.01 were considered significant. MicroRNAs with minor expression (Ct-value & gt;20) were not included. Putative targets of dysregulated microRNAs were considered, if predicted by at least three databases, and further analyzed using the DAVID-bioinformatic database. Results: Four microRNAs were significantly deregulated (miR-7, miR-744*, miR-616, miR-212) between responders and non-responders, when being treatment-naïve, predicted to have 97 potential targets. In depth target analysis showed that transcription regulators (21% of the predicted targets) are highly enriched compared to normal gene expression background of humans. Pathway analysis revealed six genes involved in cancer pathways, whereas four of them are directly involved in the chronic myeloid leukemia pathway (SMAD4, NRAS, RB1, RAF1). In responders seven microRNAs were deregulated before and after therapy, whereas five other microRNAs were deregulated within the group of non-responders. Three deregulated microRNAs were identified in both groups. Most predicted target genes are involved in MAPK signaling and exocytosis, 13% of the targets were predicted to be transcription regulators, and 18% cellular (especially uptake) transporters. Conclusion: We identified distinct microRNA pattern comparing blood samples of responders and non-responders prior to imatinib therapy. Predicted target genes were primarily transcription factors and oncogenes. In contrast, transporters and exocytotic pathways are in addition frequent targets of microRNAs deregulated after imatinib therapy. The suitability as biomarkers for prediction of imatinib-response requires further confirmation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1097. doi:1538-7445.AM2012-1097
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-1097
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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