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Frequent STAT5B mutations in γδ hepatosplenic T-cell lymphomas

Leukemia volume 28, pages 2244–2248 (2014)Cite this article

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Hepatosplenic T-cell lymphomas (HSTCL) account for <1% of all non-Hodgkin’s lymphomas. These rare T-cell lymphomas primarily affect young males, display aggressive behavior and have a dismal prognosis.1 Patients present with B-symptoms, hepatosplenomegaly, cytopenias and bone marrow infiltration in the absence of both lymphadenopathy and peripheral blood involvement. Most cases are believed to arise from γδ T cells resident in the spleen and diffusely involve splenic and hepatic sinuses. Accordingly, HSTCL are most commonly TCRγδ+, TCRβ−, CD4–/CD8–, CD5–, CD56+, TIA1+, perforin− and granzyme B−, the latter markers being indicators of an immature cytotoxic T-cell phenotype.

Little is known about the etiology and pathobiology of this lymphoma, in part due to its rarity. Its prevalence in patients with autoimmune disease treated with anti-TNFα and in immunosuppressed transplant recipients suggests that chronic antigenic stimulation and immune system impairment might play some role in its genesis.1 Cytogenetic studies indicate a high frequency of nonrandom chromosomal abnormalities, including isochromosome 7q [i(7)(q10)], trisomy 8 (8+) or loss of the Y chromosome,2 but the genes involved in neoplastic transformation are as yet unknown. Gene expression profiling studies report an NK/T cell lymphoma-like signature, and overexpression of several genes including multidrug resistance genes (MDR1), cell trafficking genes (S1PR5) and growth and survival genes (SYK). Interestingly, significant enrichment of genes involved in JAK/STAT signaling was also observed.3

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Acknowledgements

We thank Shahed Abdullah, personnel of the Immunohistochemistry Unit, and the Molecular Diagnostics Unit for their expert technical assistance. 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. Hematopathology Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    A Nicolae, S Pittaluga & E S Jaffe

  2. Molecular Diagnostics Unit, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    L Xi & M Raffeld

  3. Chromosome Biology Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Z Abdullaev & S D Pack

  4. Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    J Chen & T A Waldmann

Authors
  1. A Nicolae
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  2. L Xi
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Corresponding author

Correspondence to M Raffeld.

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The authors declare no conflict of interest.

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Author Contributions

All authors were involved in the design and approval of the final manuscript. AN performed the experiments, analyzed the data and wrote the manuscript; LX designed the primers, performed the experiments and analyzed the data; SP and ZA performed and interpreted the FISH analysis; MR supervised the work and wrote the manuscript; SP, ESJ, AN and MR confirmed the histopathological diagnoses.

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Nicolae, A., Xi, L., Pittaluga, S. et al. Frequent STAT5B mutations in γδ hepatosplenic T-cell lymphomas. Leukemia 28, 2244–2248 (2014). https://doi.org/10.1038/leu.2014.200

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