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NPM-ALK expression levels identify two distinct subtypes of paediatric anaplastic large cell lymphoma

Leukemia volume 31, pages 498–501 (2017)Cite this article

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Anaplastic large cell lymphoma (ALCL) is a distinct form of non-Hodgkin lymphoma that accounts for 10–15% of all childhood lymphomas. Differently from ALCL in adults, where about 30% of cases are ALK+, ALCL in children is nearly universally ALK+, and in almost all of the cases, it is characterized by the t(2;5)(p23;q35) translocation, which results in the expression of the hybrid oncogenic tyrosine kinase NPM-ALK.1 NPM-ALK fusion protein is responsible for ALCL development, and throughout its constitutive tyrosine kinase activity, it regulates signalling pathways critical for proliferation, cell-cycle control and survival of ALCL cells.2 So far, few studies have investigated ALCL gene expression profiling, and most of them have used heterogeneous populations of paediatric and adult cases.3 Main aim of such studies was to identify whether ALK+ and ALK− ALCL had a different transcriptional programme, and although differences were found, similarities were also detected.3, 4 Based on the fact that paediatric ALCL are almost exclusively ALK+, our study focussed on investigating the potential heterogeneity inside ALK+ ALCL rather than differences between ALK+ and ALK− tumours.

In order to investigate the transcriptional characteristics of ALK+ ALCL, we performed a global microarray-based transcriptional analysis on 23 paediatric tumour samples, 12 reactive lymph nodes and 4 ALCL cell lines (3 ALK+ and 1 ALK−) (Supplementary Materials). As previously reported, we found that ALK+ tumours displayed downregulation of both B-cell and T-cell receptor signalling molecules (such as ARNT2, CD3G, CD24, CD27, CD40, CD79A, NFATC2, PIK3CD, TNFRSF10A) in addition to T helper cell surface molecules (such as CD19, CD28, CTLA4), (Supplementary Table S1), consistent with the notion that this malignancy originates from undifferentiated normal CD4+ T lymphocytes.5

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Acknowledgements

This study was supported by Fondazione Città Della Speranza, Fondazione CA.RI.PA.RO. (grant 13/06) and Camera di Commercio di Venezia.

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Author notes

  1. P Bonvini and L Mussolin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Women’s and Children’s Health, Clinic of Pediatric Hemato-Oncology, University of Padova, Padova, Italy

    E Pomari, G Basso, S Bresolin, M Pillon, E Carraro, G Viola & L Mussolin

  2. Istituto di Ricerca Pediatrica, Fondazione Città della Speranza, Padova, Italy

    E Pomari, S Bresolin, G Viola, C Frasson, P Bonvini & L Mussolin

  3. Institute of Pathology, San Bortolo Hospital, Vicenza, Italy

    E S d'Amore

  4. Department of Pathology and Cell Biology, Institute for Cancer Genetics, Columbia University, New York, NY, USA

    K Basso

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  1. E Pomari
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Correspondence to L Mussolin.

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Supplementary Information accompanies this paper on the Leukemia website

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Pomari, E., Basso, G., Bresolin, S. et al. NPM-ALK expression levels identify two distinct subtypes of paediatric anaplastic large cell lymphoma. Leukemia 31, 498–501 (2017). https://doi.org/10.1038/leu.2016.292

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