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Lymphoma

Stat3 mutations impact on overall survival in large granular lymphocyte leukemia: a single-center experience of 205 patients

Leukemia volume 34, pages 1116–1124 (2020)Cite this article

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Abstract

Large granular lymphocyte leukemia (LGLL) is a rare and chronic lymphoproliferative disorder characterized by the clonal expansion of LGLs. LGLL patients can be asymptomatic or develop cytopenia, mostly neutropenia. Somatic STAT3 and STAT5b mutations have been recently reported in approximately 40% of patients. The aim of this study is to analyze clinical and biological features of a large cohort of LGLL patients to identify prognostic markers affecting patients’ outcome. In 205 LGLL patients, neutropenia (ANC < 1500/mm3) was the main feature (38%), with severe neutropenia (ANC < 500/mm3) being present in 20.5% of patients. STAT3 mutations were detected in 28.3% patients and were associated with ANC < 500/mm3 (p < 0.0001), Hb < 90 g/L (p = 0.0079) and treatment requirement (p < 0.0001) while STAT5b mutations were found in 15/152 asymptomatic patients. By age-adjusted univariate analysis, ANC < 500/mm3 (p = 0.013), Hb < 90 g/L (p < 0.0001), treatment requirement (p = 0.001) and STAT3 mutated status (p = 0.011) were associated to reduced overall survival (OS). By multivariate analysis, STAT3 mutated status (p = 0.0089) and Hb < 90 g/L (p = 0.0011) were independently associated to reduced OS. In conclusion, we identified clinical and biological features associated to reduced OS in LGLL and we demonstrated the adverse impact of STAT3 mutations in patients’ survival, suggesting that this biological feature should be regarded as a potential target of therapy.

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Acknowledgements

The authors would like to thank Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 2017-20216).

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Authors and Affiliations

  1. Department of Medicine (DIMED), Hematology and Clinical Immunology Section, Padua University School of Medicine, Padua, Italy

    Gregorio Barilà, Antonella Teramo, Giulia Calabretto, Cristina Vicenzetto, Vanessa Rebecca Gasparini, Laura Pavan, Matteo Leoncin, Susanna Vedovato, Monica Facco, Gianpietro Semenzato & Renato Zambello

  2. Veneto Institute of Molecular Medicine (VIMM), Padua, Italy

    Gregorio Barilà, Antonella Teramo, Giulia Calabretto, Cristina Vicenzetto, Vanessa Rebecca Gasparini, Monica Facco, Gianpietro Semenzato & Renato Zambello

  3. Department of Cardiac-Thoracic-Vascular Sciences and Public Health, Biostatistics, Epidemiology and Public Health Unit, Padua University School of Medicine, Padua, Italy

    Anna Chiara Frigo

Authors
  1. Gregorio Barilà
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  2. Antonella Teramo
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  3. Giulia Calabretto
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  4. Cristina Vicenzetto
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  5. Vanessa Rebecca Gasparini
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  6. Laura Pavan
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  9. Anna Chiara Frigo
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  10. Monica Facco
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  11. Gianpietro Semenzato
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  12. Renato Zambello
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Contributions

GB designed the research, analyzed data and wrote the manuscript. AT, GC, CV and VRG performed mutations analysis. LP, ML and SV provided patient’s samples and patient’s data. MF contributed to analyze data. ACF performed statistical analysis. GS provided funding, participated in the analysis of data and critically reviewed and edited the manuscript. RZ designed the study, analyzed data, wrote the manuscript and supervised the study.

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Correspondence to Gianpietro Semenzato or Renato Zambello.

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Barilà, G., Teramo, A., Calabretto, G. et al. Stat3 mutations impact on overall survival in large granular lymphocyte leukemia: a single-center experience of 205 patients. Leukemia 34, 1116–1124 (2020). https://doi.org/10.1038/s41375-019-0644-0

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