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Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas

Leukemia volume 30, pages 2245–2247 (2016)Cite this article

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Primary intestinal T-cell lymphomas (ITCLs) comprise mainly the enteropathy-associated T-cell lymphomas (EATL). EATL is an aggressive, rare lymphoma, which represents ~5% of mature T-cell lymphomas.1 Two subtypes are recognized based on distinct morphology, immunophenotype and epidemiology. EATL type I (EATL I) is more common in Western countries, is highly associated with celiac disease (CD) and shows a phenotype akin to that of the majority normal TCRαβ+ intraepithelial lymphocytes (IEL). EATL type II (EATL II) is more frequent in Asia, is uncommon in patients with CD and is usually derived from TCRγδ+ IELs.2, 3 Both are CD3 positive and express cytotoxic markers, but though EATL I is typically CD8 and CD56 negative, EATL II is generally CD8 and CD56 positive.

The mechanisms and genetic aberrations responsible for malignant transformation are largely unknown, owing to the rarity of these lymphomas. Comparative genomic hybridization microarray studies show multiple genomic imbalances, with common gains on chromosome 1q and 5q in EATL I, gains of 8q24 in EATL II and a high prevalence of 9q gains/16q losses in both subtypes.3, 4 Until recently, there were few genetic/genomic studies of these lymphomas with the exceptions of a study of natural killer (NK)/T and γδ T-cell lymphomas that included cases of γδ EATL II,5 and a second more comprehensive study of EATL II.6 Both groups reported a high incidence of STAT5B mutations in EATL II, whereas the second group also identified frequent mutations of JAK3 and the α G-protein subunit GNAI2, as well as some less common mutations. To further understand the molecular pathogenesis of these rare lymphomas, we analyzed our own series of primary ITCL, which included EATL I, EATL II and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), by targeted next generation sequencing (NGS) of genes associated with T-cell neoplasia and proliferation.

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Acknowledgements

We thank Alexandru Ionita for helping in the design of Figure 1, Dr Laura Wake for assisting with the GNAI2 study and Dr Warren Leonard for critically reviewing the manuscript. This study was supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.

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Authors and Affiliations

  1. Laboratory of Pathology, Hematopathology Section, Center for Cancer Research, National, Cancer Institute, Bethesda, MD, USA

    A Nicolae, S Pittaluga & E S Jaffe

  2. Laboratory of Pathology, Molecular Diagnostics Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    L Xi, T H Pham, T-A Pham, W Navarro, H G Meeker & M Raffeld

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  1. A Nicolae
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  2. L Xi
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Correspondence to M Raffeld.

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Nicolae, A., Xi, L., Pham, T. et al. Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia 30, 2245–2247 (2016). https://doi.org/10.1038/leu.2016.178

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