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Cytogenetics and Molecular Genetics

Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia

Leukemia volume 23, pages 313–322 (2009)Cite this article

Abstract

MicroRNAs (miRNAs) control the expression of protein-coding genes in normal hematopoietic cells and, consequently, aberrant expression may contribute to leukemogenesis. To identify miRNAs relevant to pediatric acute lymphoblastic leukemia (ALL), we cloned 105 known and 8 new miRNA genes expressed in patients’ leukemia cells. Instead of known miRNA genes, new miRNA genes were not evolutionarily conserved. Quantification of 19 selected miRNA genes revealed an aberrant expression in ALL as compared with normal CD34+ cells (P⩽0.02); both upregulated (14/19) and downregulated (5/19) expressions were observed. Eight miRNAs were differentially expressed between MLL and non-MLL precursor B-ALL cases (P<0.05). Most remarkably, miR-708 was 250- up to 6500-fold higher expressed in 57 TEL-AML1, BCR-ABL, E2A-PBX1, hyperdiploid and B-other cases than in 20 MLL-rearranged and 15 T-ALL cases (0.0001< P<0.01), whereas the expression of miR-196b was 500-fold higher in MLL-rearranged and 800-fold higher in 5 of 15 T-ALL cases as compared with the expression level in the remaining precursor B-ALL cases (P<0.001). The expression did not correlate with the maturation status of leukemia cells based on immunoglobulin and T-cell receptor rearrangements, immunophenotype or MLL-fusion partner. In conclusion, we identified new miRNA genes and showed that miRNA expression profiles are ALL subtype-specific rather than linked to the differentiation stadium associated with these subtypes.

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Acknowledgements

We highly appreciate the contribution of CZ Chen (Department of Microbiology and Immunology, Stanford University, USA) for sharing knowledge and technologies to clone miRNAs, for performing computational analyses of miRNA structures as well as for discussing study results. We also thank the members of the COALL study group (headed by GE Janka-Schaub, Hamburg, Germany) and the Interfant study group (headed by R Pieters, Erasmus MC, Rotterdam, NL) for supporting this study with patient samples. We are grateful to MWJC Jansen (Department of Immunology, Erasmus MC, Rotterdam, NL) for providing the maturation status of MLL-rearranged cases. This study was financially supported by the Dutch Cancer Society (Program Grant EUR 2005-3662; MLdB/RP), The Netherlands Organization for Scientific Research (NWO-Vidi Grant; MLdB) and the Baxter foundation (Chen CZ).

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Authors and Affiliations

  1. Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands

    D Schotte, M J C Broekhuis, T C J M Peters, R Pieters & M L den Boer

  2. Department of Microbiology and Immunology, Baxter Laboratory of Genetic Pharmacology, Stanford University School of Medicine, Institute for Cancer, Stem Cell Biology and Medicine, Stanford, CA, USA

    J C K Chau, G Sylvester & G Liu

  3. Applied Biosystems, Foster City, CA, USA

    C Chen

  4. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    V H J van der Velden

  5. Interfant-99 Collaborative Study Group,

    R Pieters

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  1. D Schotte
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  4. G Liu
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Correspondence to M L den Boer.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Schotte, D., Chau, J., Sylvester, G. et al. Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia. Leukemia 23, 313–322 (2009). https://doi.org/10.1038/leu.2008.286

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