Defining TCRγδ lymphoproliferative disorders by combined immunophenotypic and molecular evaluation

Antonella Teramo, Andrea Binatti, Elena Ciabatti, Gianluca Schiavoni, Giulia Tarrini, Gregorio Barilà, Giulia Calabretto, Cristina Vicenzetto, Vanessa Rebecca Gasparini, Monica Facco, Iacopo Petrini, Roberto Grossi, Nadia Pisanti, Stefania Bortoluzzi, Brunangelo Falini, Enrico Tiacci, Sara Galimberti, Gianpietro Semenzato () and Renato Zambello ()
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Antonella Teramo: Padova University School of Medicine
Andrea Binatti: University of Padova
Elena Ciabatti: University of Pisa
Gianluca Schiavoni: University and Hospital of Perugia
Giulia Tarrini: University of Pisa
Gregorio Barilà: Padova University School of Medicine
Giulia Calabretto: Padova University School of Medicine
Cristina Vicenzetto: Padova University School of Medicine
Vanessa Rebecca Gasparini: Padova University School of Medicine
Monica Facco: Padova University School of Medicine
Iacopo Petrini: University of Pisa
Roberto Grossi: University of Pisa
Nadia Pisanti: University of Pisa
Stefania Bortoluzzi: University of Padova
Brunangelo Falini: University and Hospital of Perugia
Enrico Tiacci: University and Hospital of Perugia
Sara Galimberti: University of Pisa
Gianpietro Semenzato: Padova University School of Medicine
Renato Zambello: Padova University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Tγδ large granular lymphocyte leukemia (Tγδ LGLL) is a rare lymphoproliferative disease, scantily described in literature. A deep-analysis, in an initial cohort of 9 Tγδ LGLL compared to 23 healthy controls, shows that Tγδ LGLL dominant clonotypes are mainly public and exhibit different V-(D)-J γ/δ usage between patients with symptomatic and indolent Tγδ neoplasm. Moreover, some clonotypes share the same rearranged sequence. Data obtained in an enlarged cohort (n = 36) indicate the importance of a combined evaluation of immunophenotype and STAT mutational profile for the correct management of patients with Tγδ cell expansions. In fact, we observe an association between Vδ2/Vγ9 clonality and indolent course, while Vδ2/Vγ9 negativity correlates with symptomatic disease. Moreover, the 7 patients with STAT3 mutations have neutropenia and a CD56-/Vδ2- phenotype, and the 3 cases with STAT5B mutations display an asymptomatic clinical course and CD56/Vδ2 expression. All these data indicate that biological characterization is needed for Tγδ-cell neoplasm definition.

Date: 2022
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DOI: 10.1038/s41467-022-31015-x

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