Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

An aberrant microRNA signature in childhood T-cell lymphoblastic lymphoma affecting CDKN1B expression, NOTCH1 and growth factor signaling pathways

Leukemia volume 28, pages 1909–1912 (2014)Cite this article

Subjects

Childhood lymphoblastic T-cell lymphoma (T-LBL) represents about one-third of pediatric non-Hodgkin’s lymphomas, and it originates from lymphoid progenitor cells arrested at early stages of T-cell maturation.1 T-LBL patients show large mediastinal masses and no, or minimal (<25%), bone marrow involvement. These represent the main clinical features that discriminate the T-LBL from T-cell acute lymphoblastic leukemia (T-ALL) patients, who conversely display massive bone marrow involvement. Although major advances toward the understanding of T-ALL molecular pathogenesis have been achieved, similar studies in T-LBL have been greatly impaired by the paucity of diagnostic tumor tissue available from pediatric T-LBL patients. We and others have started to investigate the molecular features of T-LBL by performing genomic and gene expression analyses.2 These studies not only recognize a number of shared features between T-LBL and T-ALL but also identify several unique characteristics, suggesting that indeed these represent two distinct malignancies.

MicroRNAs (miRNAs) have been implicated in development and tumorigenesis; nevertheless their role in hematopoietic malignancies remains largely unknown, with only a few miRNAs being functionally characterized and demonstrated to act as tumor suppressors or oncogenes. Here, we report the first characterization of childhood T-LBL by miRNA expression profiling; we identify miRNAs that are de-regulated in the lymphoma cells compared with their normal counterpart and provide evidences of their function in contributing to the malignant transformation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Burkhardt B . Paediatric lymphoblastic T-cell leukaemia and lymphoma: one or two diseases? Br J Haematol. 2010; 149: 653–668.

    Article  CAS  Google Scholar 

  2. Basso K, Mussolin L, Lettieri A, Brahmachary M, Lim WK, Califano A et al. T-cell lymphoblastic lymphoma shows differences and similarities with T-cell acute lymphoblastic leukemia by genomic and gene expression analyses. Genes Chromosomes Cancer 2011; 50: 1063–1075.

    Article  CAS  Google Scholar 

  3. Ghisi M, Corradin A, Basso K, Frasson C, Serafin V, Mukherjee S et al. Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood 2011; 117: 7053–7062.

    Article  CAS  Google Scholar 

  4. Betel D, Koppal A, Agius P, Sander C, Leslie C . Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 2010; 11: R90.

    Article  Google Scholar 

  5. Huang da W, Sherman BT, Lempicki RA . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44–57.

    Article  Google Scholar 

  6. Ehnman M, Ostman A . Therapeutic targeting of platelet-derived growth factor receptors in solid tumors. Expert Opin Investig Drugs 2013; 23: 211–226.

    Article  Google Scholar 

  7. Yang J, Liu X, Nyland SB, Zhang R, Ryland LK, Broeg K et al. Platelet-derived growth factor mediates survival of leukemic large granular lymphocytes via an autocrine regulatory pathway. Blood 2010; 115: 51–60.

    Article  CAS  Google Scholar 

  8. le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. Embo J 2007; 26: 3699–3708.

    Article  CAS  Google Scholar 

  9. Gimenes-Teixeira HL, Lucena-Araujo AR, Dos Santos GA, Zanette DL, Scheucher PS, Oliveira LC et al. Increased expression of miR-221 is associated with shorter overall survival in T-cell acute lymphoid leukemia. Exp Hematol Oncol 2013; 2: 10.

    Article  CAS  Google Scholar 

  10. Mavrakis KJ, Van Der Meulen J, Wolfe AL, Liu X, Mets E, Taghon T et al. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL). Nat Genet 2011; 43: 673–678.

    Article  CAS  Google Scholar 

  11. Mansour MR, Sanda T, Lawton LN, Li X, Kreslavsky T, Novina CD et al. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. J Exp Med 2013; 210: 1545–1557.

    Article  CAS  Google Scholar 

  12. Xu Y, Sengupta T, Kukreja L, Minella AC . MicroRNA-223 regulates cyclin E activity by modulating expression of F-box and WD-40 domain protein 7. J Biol Chem 2010; 285: 34439–34446.

    Article  CAS  Google Scholar 

  13. Shaham L, Binder V, Gefen N, Borkhardt A, Izraeli. S . MiR-125 in normal and malignant hematopoiesis. Leukemia 2012; 26: 2011–2018.

    Article  CAS  Google Scholar 

  14. Song SJ, Ito K, Ala U, Kats L, Webster K, Sun SM et al. The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell 2013; 13: 87–101.

    Article  CAS  Google Scholar 

  15. Kim SW, Ramasamy K, Bouamar H, Lin AP, Jiang D, Aguiar RC . MicroRNAs miR-125a and miR-125b constitutively activate the NF-kappaB pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). Proc Natl Acad Sci USA 2012; 109: 7865–7870.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Friederike H Schwartz for technical support. This study was supported by grants to LM and MP from Fondazione Citta’ Della Speranza and Camera di Commercio di Venezia. KB is supported by The Alexander and Margaret Stewart Trust.

Author information

Author notes

  1. A Rosolen and K Basso: Deceased.

Authors and Affiliations

  1. Istituto di Ricerca Pediatrico Fondazione Citta’ della Speranza, Padova, Italy

    L Mussolin & A Rosolen

  2. Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Universita’ di Padova, Padova, Italy

    L Mussolin, M Pillon & A Rosolen

  3. Institute for Cancer Genetics, Columbia University, New York, NY, USA

    A B Holmes & K Basso

  4. Department of Biology, University of Padova, Padova, Italy

    C Romualdi & G Sales

  5. Department of Pathology, San Bortolo Hospital, Vicenza, Italy

    E S G D'Amore

  6. Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy

    M Ghisi

  7. Department of Pathology and Cell Biology, Columbia University, New York, NY, USA

    K Basso

Authors
  1. L Mussolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A B Holmes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Romualdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Sales
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E S G D'Amore
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Ghisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Pillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Rosolen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K Basso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Basso.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mussolin, L., Holmes, A., Romualdi, C. et al. An aberrant microRNA signature in childhood T-cell lymphoblastic lymphoma affecting CDKN1B expression, NOTCH1 and growth factor signaling pathways. Leukemia 28, 1909–1912 (2014). https://doi.org/10.1038/leu.2014.134

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2014.134

This article is cited by

Search

Advanced search

Quick links