Expression patterns of microRNAs associated with CML phases and their disease related targets

Molecular Cancer

Research

Tomáš Stopka¹  Pavel Burda¹  Kateřina Machová Poláková²  Hana Klamová²  Marek Trněný²  Jana Moravcová²  Tereza Lopotová³ 

[1] First Faculty of Medicine and Center of Experimental Hematology, Charles University in Prague, U Nemocnice 5, 128 53, Czech Republic;Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20, Prague, Czech Republic;Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20, Prague, Czech Republic;The Faculty of Science, Charles University, Viničná 5, 128 00, Prague, Czech Republic;

关键词: Imatinib;    Chronic Lymphocytic Leukemia;    Chronic Myeloid Leukemia;    Chronic Myeloid Leukemia Patient;    Blast Crisis;   

DOI  :  10.1186/1476-4598-10-41

 received in 2010-11-30, accepted in 2011-04-18,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundMicroRNAs are important regulators of transcription in hematopoiesis. Their expression deregulations were described in association with pathogenesis of some hematological malignancies. This study provides integrated microRNA expression profiling at different phases of chronic myeloid leukemia (CML) with the aim to identify microRNAs associated with CML pathogenesis. The functions of in silico filtered targets are in this report annotated and discussed in relation to CML pathogenesis.ResultsUsing microarrays we identified differential expression profiles of 49 miRNAs in CML patients at diagnosis, in hematological relapse, therapy failure, blast crisis and major molecular response. The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR. In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK), epidermal growth factor receptor (EGFR, ERBB), transforming growth factor beta (TGFB1) and tumor protein p53 that are all related to CML. Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level.ConclusionsThis study uncovers microRNAs that are potentially involved in CML and the annotated functions of in silico filtered targets of selected miRNAs outline mechanisms whereby microRNAs may be involved in CML pathogenesis.

【 授权许可】

Unknown   
© Poláková et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.