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Acute Leukemias

Specific small nucleolar RNA expression profiles in acute leukemia

Leukemia volume 26, pages 2052–2060 (2012)Cite this article

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Abstract

Apart from microRNAs, little is known about the regulation of expression of non-coding RNAs in cancer. We investigated whether small nucleolar RNAs (snoRNAs) accumulation displayed specific signatures in acute myeloblastic and acute lymphoblastic leukemias. Using microarrays and high-throughput quantitative PCR (qPCR), we demonstrate here that snoRNA expression patterns are negatively altered in leukemic cells compared with controls. Interestingly, a specific signature was found in acute promyelocytic leukemia (APL) with ectopic expression of SNORD112–114 snoRNAs located at the DLK1-DIO3 locus. In vitro experiments carried out on APL blasts demonstrate that transcription of these snoRNAs was lost under all-trans retinoic acid-mediated differentiation and induced by enforced expression of the PML–RARalpha fusion protein in negative leukemic cell lines. Further experiments revealed that the SNORD114-1 (14q(II-1)) variant promoted cell growth through cell cycle modulation; its expression was implicated in the G0/G1 to S phase transition mediated by the Rb/p16 pathways. This study thus reports three important observations: (1) snoRNA regulation is different in normal cells compared with cancer cells; (2) a relationship exists between a chromosomal translocation and expression of snoRNA loci; and (3) snoRNA expression can affect Rb/p16 cell cycle regulation. Taken together, these data strongly suggest that snoRNAs have a role in cancer development.

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Acknowledgements

We are grateful to the patients who participated in this study and their referring physicians. We thank the Genotoul platform, Toulouse, France (Naïs Prade and Jean-José Maoret). We also thank Valerie Lallemand-Breitenbach, José Ángel Martínez Climent and Pauline Gravelle for their helpful comments on this work. This study was supported by grants from the Institut Universitaire de France, the Association pour la Recherche sur le Cancer (ARC) and the CITTIL program (Cooperación de Investigación Transpirenaica en la Terapia Innovadora de la Leucemia).

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Authors and Affiliations

  1. INSERM UMR1037-Cancer Research Center of Toulouse, University of Toulouse III, Toulouse, France

    W Valleron, E Laprevotte, E-F Gautier, C Quelen, C Demur, E Delabesse & P Brousset

  2. Department of Hematology, CHU Purpan, Toulouse, France

    C Demur & E Delabesse

  3. CIMA, Pamplona, Spain

    X Agirre & F Prósper

  4. LBME CNRS UMR 5099, University Paul Sabatier, Toulouse, France

    T Kiss

  5. Department of Pathology, CHU Purpan, Toulouse, France

    P Brousset

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  1. W Valleron
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Correspondence to P Brousset.

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Valleron, W., Laprevotte, E., Gautier, EF. et al. Specific small nucleolar RNA expression profiles in acute leukemia. Leukemia 26, 2052–2060 (2012). https://doi.org/10.1038/leu.2012.111

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