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Computational dissection of distinct microRNA activity signatures associated with peripheral T cell lymphoma subtypes

Leukemia volume 27, pages 2107–2111 (2013)Cite this article

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In hematological malignancies, various studies on microRNA (miRNA) profiling have highlighted specific miRNA signatures associated with several clinical conditions, such as disease subtypes, drug responses, and clinical outcomes in leukemia and B cell lymphomas, in parallel with the mRNA profiling study.1, 2 On the other hand, the characterization of these disease-related miRNA signatures is often compromised by the poor overlapping results of multiple independent studies, even if they focused on the same disease.3, 4 This problem may be partly explained by a poor overlap among differentially expressed miRNAs identified by multiple miRNA microarray platforms.4 One promising approach is the paired profiling of mRNAs and miRNAs, and integrated analysis of both to extract disease-related features. Although the pairing of miRNAs and target mRNAs can be inferred from anticorrelation between miRNAs and mRNAs, the generally weak impacts of miRNAs on mRNA expression levels still make this approach difficult.

Recent miRNA profiling in anaplastic large cell lymphoma (ALCL) showed dysregulated miRNA profiles, including miR-17–92 cluster, miR-106a and miR-155, between anaplastic lymphoma kinase (ALK)+ and ALK− ALCLs.6 In addition, we and another group reported miR-135b upregulation and miR-29a downregulation in ALK+ ALCL, respectively.7, 8 We used the results of comprehensive gene expression profiling on 144 PTCL patients, including AITL, ALK+ ALCL, ALK− ALCL, adult T cell leukemia/lymphoma (ATLL) and PTCL not-otherwise-specified (PTCL-NOS).9 We performed GFA between ALK+ ALCL and ALK− ALCL, and between ALK+ ALCL and all PTCL cases so that GFA could be applied for more than two groups. GFA results successfully predicted high activity of miR-106 and miR-135 and low activity of miR-29 in ALK+ ALCL both in comparison with ALK− ALCL and with all cases (Figure 1b). In miR-17–92 cluster, miR-19 was predicted to be active.

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Acknowledgements

We thank Nishimori H, Morishita Y and Mihira H for their discussion and skilled technical assistance; and all the members of the Department of Molecular Pathology, the University of Tokyo. This work was supported by KAKENHI (Grants-in-Aid for Young Scientists (A) (no. 24689018) and for Scientific Research on Innovative Areas ‘RNA regulation’ (no. 23112702), and ‘Integrative research on cancer microenvironment network’ (no. 22112002)), the Global Center of Excellence Program for ‘Integrative Life Science Based on the Study of Biosignaling Mechanisms’ from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Cell Science Research Foundation.

Author contributions

HIS designed the research, performed experiments and analyses, and wrote the paper; HM provided the key materials, and performed the experiments and analyses; MN, TY, NK and KS provided clinical samples; and KS and KM supervised the project and wrote the paper.

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Authors and Affiliations

  1. Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan

    H I Suzuki, H Matsuyama & K Miyazono

  2. Department of Hematology, Juntendo Urayasu Hospital, Urayasu-shi, Japan

    M Noguchi

  3. Department of Human Pathology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Japan

    T Yao

  4. Division of Hematology, Department of Internal Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Japan

    N Komatsu & K Sugimoto

  5. Department of Medical Genomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan

    H Mano

  6. Division of Functional Genomics, Jichi Medical University, Shimotsuke-shi, Japan

    H Mano

  7. Department of Hematology and Oncology, JR Tokyo General Hospital, Shibuya-ku, Japan

    K Sugimoto

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  1. H I Suzuki
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Correspondence to H I Suzuki or K Miyazono.

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Suzuki, H., Matsuyama, H., Noguchi, M. et al. Computational dissection of distinct microRNA activity signatures associated with peripheral T cell lymphoma subtypes. Leukemia 27, 2107–2111 (2013). https://doi.org/10.1038/leu.2013.121

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