MicroRNAs Distinguish Cytogenetic Subgroups in Pediatric AML and Contribute to Complex Regulatory Networks in AML-Relevant Pathways

Daschkey, Svenja; Rƶttgers, Silja; Giri, Anamika; Bradtke, Jutta; Teigler-Schlegel, Andrea; Meister, Gunter; Borkhardt, Arndt; Landgraf, Pablo
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Background: The role of microRNAs (miRNAs), important post-transcriptional regulators, in the pathogenesis of acute myeloid leukemia (AML) is just emerging and has been mainly studied in adults. First studies in children investigate single selected miRNAs, however, a comprehensive overview of miRNA expression and function in children and young adults is missing so far. Methodology/Principal Findings: We here globally identified differentially expressed miRNAs between AML subtypes in a survey of 102 children and adolescent. Pediatric samples with core-binding factor AML and promyelocytic leukemia could be distinguished from each other and from MLL-rearranged AML subtypes by differentially expressed miRNAs including miR-126, -146a, -181a/b, -100, and miR-125b. Subsequently, we established a newly devised immunoprecipitation assay followed by rapid microarray detection for the isolation of Argonaute proteins, the hallmark of miRNA targeting complexes, from cell line models resembling core-binding factor and promyelocytic leukemia. Applying this method, we were able to identify Ago-associated miRNAs and their targeted mRNAs. Conclusions/Significance: miRNAs as well as their mRNA-targets showed binding preferences for the different Argonaute proteins in a cell context-dependent manner. Bioinformatically-derived pathway analysis suggested a concerted action of all four Argonaute complexes in the regulation of AML-relevant pathways. For the first time, to our knowledge, a complete AML data set resulting from carefully devised biochemical isolation experiments and analysis of Ago-associated miRNAs and their target-mRNAs is now available.


Related Articles

  • The Transcriptome Study of Subtype M2 Acute Myeloblastic Leukemia. Wu, A-yang; Yang, Hui-cong; Lin, Cong-meng; Wu, Bi-de; Qu, Qi-shui; Zheng, Yuan-hai; Wei, Hua; Mei, Xu-qiao; Zeng, Zhen-hua; Ma, Xu-dong // Cell Biochemistry & Biophysics;Jul2015, Vol. 72 Issue 3, p653 

    Our objective is to explore the tumor-specific mutated genes by transcriptome sequencing of patients with acute myeloblastic leukemia. 96 patients with subtype M2 acute myeloid leukemia (AML), admitted during January 2007 to January 2012, were selected. Bone marrow and peripheral blood samples...

  • Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia. Alachkar, Houda; Santhanam, Ramasamy; Harb, Jason G.; Lucas, David M.; Oaks, Joshua J.; Hickey, Christopher J.; Pan, Li; Kinghorn, A. Douglas; Caligiuri, Michael A.; Perrotti, Danilo; Byrd, John C.; Garzon, Ramiro; Grever, Michael R.; Marcucci, Guido // Journal of Hematology & Oncology;2013, Vol. 6 Issue 1, p1 

    Background: Activating mutations [internal tandem duplication (ITD)] or overexpression of the FMS-like tyrosine kinase receptor-3 (FLT3) gene are associated with poor outcome in acute myeloid leukemia (AML) patients, underscoring the need for novel therapeutic approaches. The natural product...

  • Targeting leukemia stem cells in vivo with antagomiR-126 nanoparticles in acute myeloid leukemia. Dorrance, A M; Neviani, P; Ferenchak, G J; Huang, X; Nicolet, D; Maharry, K S; Ozer, H G; Hoellarbauer, P; Khalife, J; Hill, E B; Yadav, M; Bolon, B N; Lee, R J; Lee, L J; Croce, C M; Garzon, R; Caligiuri, M A; Bloomfield, C D; Marcucci, G // Leukemia (08876924);Nov2015, Vol. 29 Issue 11, p2143 

    Current treatments for acute myeloid leukemia (AML) are designed to target rapidly dividing blast populations with limited success in eradicating the functionally distinct leukemia stem cell (LSC) population, which is postulated to be responsible for disease resistance and relapse. We have...

  • Rare cytogenetic abnormalities and alteration of microRNAs in acute myeloid leukemia and response to therapy. Shahjahani, Mohammad; Khodadi, Elahe; Seghatoleslami, Mohammad; Asl, Javad Mohammadi; Golchin, Neda; Zaieri, Zeynab Deris; Saki, Najmaldin // Oncology Reviews;2015, Vol. 9 Issue 1, p7 

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults, which is heterogeneous in terms of morphological, cytogenetic and clinical features. Cytogenetic abnormalities, including karyotype aberrations, gene mutations and gene expression abnormalities are the most important...

  • c-Myc modulates microRNA processing via the transcriptional regulation of Drosha. Xingwu Wang; Xiaocheng Zhao; Ping Gao; Mian Wu // Scientific Reports;6/7/2013, p1 

    The c-Myc oncogenic transcription factor is known to regulate microRNA (miRNA) expression at the transcriptional level. However, little is known about the function of c-Myc in miRNA processing. Here, we report that Drosha, one of the most important components of the miRNA processing machinery,...

  • Differentiation and Cell Survival of Myeloid Leukemia Cells. Studzinski, George P.; Brown, Geoffrey; Danilenko, Michael; Hughes, Philip; Marcinkowska, Ewa // Leukemia Research & Treatment;2012, p1 

    An introduction is presented in which the editor discusses various reports within the issue on topics including treatment of acute myeloid leukemia, transcription factors and cell differentiation.

  • The Histone Code and Treatments for Acute Myeloid Leukemia. Godley, Lucy A.; Le Beau, Michelle M. // New England Journal of Medicine;3/8/2012, Vol. 366 Issue 10, p960 

    The article focuses on the histone code and treatments for acute myeloid leukemia. Several short hairpin RNA designed to reduce the expression of BRD4, a gene encoding a protein that recognizes acetylated histones, were found to inhibit the growth of an MLL-associated acute myeloid leukemia and...

  • Assessing 'Cure' in AML. Ershler, William B. // Clinical Oncology Alert;Jan2008, Vol. 24 Issue 1, p6 

    Although the majority of patients with acute myeloid leukemia (AML) achieve complete remission following standard induction chemotherapy with agents such as daunorubicin and cytosine arabinoside, most will relapse and relatively few are cured. Clinicians are well aware that cytogenetic...

  • Cytarabine/gemtuzumab ozogamicin.  // Reactions Weekly;3/9/2013, Issue 1443, p13 

    An abstract of the article "High response rate for treatment with gemtuzumab ozogamicin and cytarabine in elderly patients with acute myeloid leukemia and favorable and intermediate-I cytogenetic risk," by S. Tavor and colleagues is presented.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics