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5. Tγδ LGLL identifies a subset with more symptomatic disease: analysis of an international cohort of 137 patients

Author

Barilà, Gregorio, Grassi, Angela, Cheon, HeeJin, Teramo, Antonella, Calabretto, Giulia, Chahal, Jasmanet, Vicenzetto, Cristina, Almeida, Julia, Shemo, Bryna C., Shi, Min, Gasparini, Vanessa Rebecca, Munoz-Garcia, Noemi, Pastoret, Cédric, Nakazawa, Hideyuki, Oshimi, Kazuo, Sokol, Lubomir, Ishida, Fumihiro, Lamy, Thierry, Orfao, Alberto, Morice, William G., Loughran, Thomas P., Jr., Semenzato, Gianpietro, and Zambello, Renato

Published
2023
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6. Hypocellular myelodysplastic syndromes (h-MDS): from clinical description to immunological characterization in the Italian multi-center experience

Author

Calabretto, Giulia, Attardi, Enrico, Teramo, Antonella, Trimarco, Valentina, Carraro, Samuela, Mossuto, Sandra, Barilà, Gregorio, Vicenzetto, Cristina, Gasparini, Vanessa Rebecca, Crugnola, Monica, Niscola, Pasquale, Poloni, Antonella, Giai, Valentina, Gaidano, Valentina, Finelli, Carlo, Bertorelle, Roberta, Candiotto, Cinzia, Pizzi, Marco, Binotto, Gianni, Facco, Monica, Vianello, Fabrizio, Trentin, Livio, Semenzato, Gianpietro, Zambello, Renato, and Santini, Valeria

Published
2022
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7. Proteasome Inhibitors Induce Apoptosis in Ex Vivo Cells of T-Cell Prolymphocytic Leukemia.

Author

Gasparini, Vanessa Rebecca, Rampazzo, Elisa, Barilà, Gregorio, Buratin, Alessia, Buson, Elena, Calabretto, Giulia, Vicenzetto, Cristina, Orsi, Silvia, Tonini, Alessia, Teramo, Antonella, Trentin, Livio, Facco, Monica, Semenzato, Gianpietro, Bortoluzzi, Stefania, and Zambello, Renato

Abstract

Finding an effective treatment for T-PLL patients remains a significant challenge. Alemtuzumab, currently the gold standard, is insufficient in managing the aggressiveness of the disease in the long term. Consequently, numerous efforts are underway to address this unmet clinical need. The rarity of the disease limits the ability to conduct robust clinical trials, making in silico, ex vivo, and in vivo drug screenings essential for designing new therapeutic strategies for T-PLL. We conducted a drug repurposing analysis based on T-PLL gene expression data and identified proteasome inhibitors (PIs) as a promising new class of compounds capable of reversing the T-PLL phenotype. Treatment of ex vivo T-PLL cells with Bortezomib and Carfilzomib, two PI compounds, supported this hypothesis by demonstrating increased apoptosis in leukemic cells. The current lack of a suitable in vitro model for the study of T-PLL prompted us to perform similar experiments in the SUP-T11 cell line, validating its potential by showing an increased apoptotic rate. Taken together, these findings open new avenues for investigating the molecular mechanisms underlying the efficacy of PI in T-PLL and expand the spectrum of potential therapeutic strategies for this highly aggressive disease. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Defining TCRγδ lymphoproliferative disorders by combined immunophenotypic and molecular evaluation

Author

Teramo, Antonella, Binatti, Andrea, Ciabatti, Elena, Schiavoni, Gianluca, Tarrini, Giulia, Barilà, Gregorio, Calabretto, Giulia, Vicenzetto, Cristina, Gasparini, Vanessa Rebecca, Facco, Monica, Petrini, Iacopo, Grossi, Roberto, Pisanti, Nadia, Bortoluzzi, Stefania, Falini, Brunangelo, Tiacci, Enrico, Galimberti, Sara, Semenzato, Gianpietro, and Zambello, Renato

Published
2022
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9. Large Granular Lymphocyte Leukemia

Author

Teramo, Antonella, Vicenzetto, Cristina, Barilà, Gregorio, Calabretto, Giulia, Gasparini, Vanessa Rebecca, Semenzato, Gianpietro, Zambello, Renato, Dreyling, Martin, Series Editor, and Ladetto, Marco, editor

Published
2021
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10. Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia

Author

Bhattacharya, Dipabarna, Teramo, Antonella, Gasparini, Vanessa Rebecca, Huuhtanen, Jani, Kim, Daehong, Theodoropoulos, Jason, Schiavoni, Gianluca, Barilà, Gregorio, Vicenzetto, Cristina, Calabretto, Giulia, Facco, Monica, Kawakami, Toru, Nakazawa, Hideyuki, Falini, Brunangelo, Tiacci, Enrico, Ishida, Fumihiro, Semenzato, Gianpietro, Kelkka, Tiina, Zambello, Renato, and Mustjoki, Satu

Published
2022
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14. Pro-inflammatory cells sustain leukemic clonal expansion in T-cell large granular lymphocyte leukemia

Author

Vicenzetto, Cristina, primary, Gasparini, Vanessa Rebecca, additional, Barila, Gregorio, additional, Teramo, Antonella, additional, Calabretto, Giulia, additional, Rampazzo, Elisa, additional, Carraro, Samuela, additional, Trimarco, Valentina, additional, Trentin, Livio, additional, Facco, Monica, additional, Semenzato, Gianpietro, additional, and Zambello, Renato, additional

Published
2023
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15. A Comprehensive, Multiomics Analysis of Natural Killer-Cell Malignancies

Author

Nygren, Petra Johanna, primary, Häkkinen, Aino, additional, Kim, Daehong, additional, Jarvinen, Timo, additional, Ishida, Fumihiro, additional, Bortoluzzi, Stefania, additional, Binatti, Andrea, additional, Gasparini, Vanessa Rebecca, additional, Zambello, Renato, additional, Myllymäki, Mikko, additional, Ogawa, Seishi, additional, Okuno, Yusuke, additional, Kimura, Hiroshi, additional, Chan, John, additional, Dufva, Olli, additional, Mustjoki, Satu, additional, and Kankainen, Matti, additional

Published
2022
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16. Tγδ LGL LEUKEMIA IDENTIFIES A SUBSET WITH MORE SYMPTOMATIC DISEASE: ANALYSIS OF AN INTERNATIONAL COHORT OF 137 PATIENTS

Author

Barila', Gregorio, primary, Grassi, Angela, additional, Cheon, HeeJin, additional, Teramo, Antonella, additional, Calabretto, Giulia, additional, Chahal, Jasmanet Singh, additional, Vicenzetto, Cristina, additional, Almeida, Julia, additional, Shemo, Bryna C, additional, Shi, Min, additional, Gasparini, Vanessa Rebecca Rebecca, additional, Munoz-Garcia, Noemi, additional, Pastoret, Cedric, additional, Nakazawa, Hideyuki, additional, Oshimi, Kazuo, additional, Sokol, Lubomir, additional, Ishida, Fumihiro, additional, Lamy, Thierry, additional, Orfao, Alberto, additional, Morice, William George, additional, Loughran, Thomas, additional, Semenzato, Gianpietro, additional, and Zambello, Renato, additional

Published
2022
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17. Atypical Mature T-Cell Neoplasms: The Relevance of the Role of Flow Cytometry

Author

Statuto, Teodora, D’Auria, Fiorella, Del Vecchio, Luigi, Mansueto, Giovanna Rosaria, Villani, Oreste, Lalinga, Anna Vittoria, Possidente, Luciana, Nozza, Filomena, Vona, Gabriella, Rago, Luciana, Storto, Giovanni, Gasparini, Vanessa Rebecca, Zambello, Renato, D’Arena, Giovanni, and Valvano, Luciana

Subjects
angioimmunoblastic t-cell lymphoma, diagnosis, peripheral t-cell lymphoma not otherwise specified, Angioimmunoblastic T-cell lymphoma, Diagnosis, Flow cytometry, Immunophenotype, Peripheral T-cell lymphoma not otherwise specified, T-cell prolymphocytic leukemia, flow cytometry, Case Series, t-cell prolymphocytic leukemia, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, OncoTargets and Therapy, immunophenotype
Abstract

Teodora Statuto,1,* Fiorella D’Auria,2,* Luigi Del Vecchio3,4,†, Giovanna Rosaria Mansueto,5 Oreste Villani,5 Anna Vittoria Lalinga6,†, Luciana Possidente,6 Filomena Nozza,1 Gabriella Vona,1 Luciana Rago,7 Giovanni Storto,8 Vanessa Rebecca Gasparini,9 Renato Zambello,10 Giovanni D’Arena,5,* Luciana Valvano1,* 1Laboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 2Unit of Clinical Pathology, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 3CEINGE Biotecnologie Avanzate S.c.a.r.l, Federico II University, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology (DMMBM), Federico II University, Naples, Italy; 5Hematology Department of Basilicata, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 6Pathology Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 7Radiotherapy Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 8Department of Nuclear Medicine, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 9Department of Medicine, University of Padova - Veneto Institute of Molecular Medicine, VIMM, Padova, PD, Italy; 10Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padova, PD, Italy†Anna Vittoria Lalinga passed away on January 26, 2020 and Luigi Del Vecchio passed away on August 16, 2018*These authors contributed equally to this workCorrespondence: Luciana ValvanoLaboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, ItalyTel +39 0972 726395Fax +39 0972 723509Email luciana.valvano@crob.itAbstract: Lymphoproliferative disorders are a heterogeneous group of malignant clonal proliferations of lymphocytes whose diagnosis remains challenging, despite diagnostic criteria are now well established, due to their heterogeneity in clinical presentation and immunophenotypic profile. Lymphoid T-cell disorders are more rarely seen than B-cell entities and more difficult to diagnose for the absence of a specific immunophenotypic signature. Flow cytometry is a useful tool in diagnosing T-cell lymphoproliferative disorders since it is not only able to better characterize T-cell neoplasms but also to resolve some very complicated cases, in particular those in which a small size population of neoplastic cells is available for the analysis. Here, we report three patients with mature T-cell neoplasms with atypical clinical and biological features in which analysis of peripheral blood and bone marrow specimens by means of multicolor flow cytometry was very useful to identify and characterize three rare T-cell lymphoproliferative disorders, such as angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified and T-cell prolymphocytic leukemia. The aim of this case series report is not only to describe three rare cases of lymphoproliferative neoplasms but also to raise awareness that a fast, highly sensitive, and reproducible procedure, such as flow cytometry immunophenotyping, can have a determinant diagnostic role in these patients.Keywords: flow cytometry, immunophenotype, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, T-cell prolymphocytic leukemia, diagnosis

Published
2020

18. Circular RNA Dysregulation Characterizes Symptomatic T-LGL Leukemia Patients with STAT3 Mutation

Author

Buratin, Alessia, primary, Vicenzetto, Cristina, additional, Gasparini, Vanessa Rebecca, additional, Binatti, Andrea, additional, Teramo, Antonella, additional, Calabretto, Giulia, additional, Barilà, Gregorio, additional, Gaffo, Enrico, additional, Piazza, Francesco, additional, Semenzato, Gianpietro, additional, Zambello, Renato, additional, and Bortoluzzi, Stefania, additional

Published
2021
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20. Treatment Induced Cytotoxic T-Cell Modulation in Multiple Myeloma Patients

Author

Barilà, Gregorio, primary, Pavan, Laura, additional, Vedovato, Susanna, additional, Berno, Tamara, additional, Lo Schirico, Mariella, additional, Arangio Febbo, Massimiliano, additional, Teramo, Antonella, additional, Calabretto, Giulia, additional, Vicenzetto, Cristina, additional, Gasparini, Vanessa Rebecca, additional, Fregnani, Anna, additional, Manni, Sabrina, additional, Trimarco, Valentina, additional, Carraro, Samuela, additional, Facco, Monica, additional, Piazza, Francesco, additional, Semenzato, Gianpietro, additional, and Zambello, Renato, additional

Published
2021
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21. Lack of Viral Load Within Chronic Lymphoproliferative Disorder of Natural Killer Cells: What Is Outside the Leukemic Clone?

Author

Giussani, Edoardo, primary, Binatti, Andrea, additional, Calabretto, Giulia, additional, Gasparini, Vanessa Rebecca, additional, Teramo, Antonella, additional, Vicenzetto, Cristina, additional, Barilà, Gregorio, additional, Facco, Monica, additional, Coppe, Alessandro, additional, Semenzato, Gianpietro, additional, Bortoluzzi, Stefania, additional, and Zambello, Renato, additional

Published
2021
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23. Atypical Mature T-Cell Neoplasms: The Relevance of the Role of Flow Cytometry

Author

Statuto,Teodora, D'Auria,Fiorella, Del Vecchio,Luigi, Mansueto,Giovanna Rosaria, Villani,Oreste, Lalinga,Anna Vittoria, Possidente,Luciana, Nozza,Filomena, Vona,Gabriella, Rago,Luciana, Storto,Giovanni, Gasparini,Vanessa Rebecca, Zambello,Renato, D'Arena,Giovanni, Valvano,Luciana, Statuto,Teodora, D'Auria,Fiorella, Del Vecchio,Luigi, Mansueto,Giovanna Rosaria, Villani,Oreste, Lalinga,Anna Vittoria, Possidente,Luciana, Nozza,Filomena, Vona,Gabriella, Rago,Luciana, Storto,Giovanni, Gasparini,Vanessa Rebecca, Zambello,Renato, D'Arena,Giovanni, and Valvano,Luciana

Abstract

Teodora Statuto,1,* Fiorella D’Auria,2,* Luigi Del Vecchio3,4,†, Giovanna Rosaria Mansueto,5 Oreste Villani,5 Anna Vittoria Lalinga6,†, Luciana Possidente,6 Filomena Nozza,1 Gabriella Vona,1 Luciana Rago,7 Giovanni Storto,8 Vanessa Rebecca Gasparini,9 Renato Zambello,10 Giovanni D’Arena,5,* Luciana Valvano1,* 1Laboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 2Unit of Clinical Pathology, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 3CEINGE Biotecnologie Avanzate S.c.a.r.l, Federico II University, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology (DMMBM), Federico II University, Naples, Italy; 5Hematology Department of Basilicata, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 6Pathology Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 7Radiotherapy Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 8Department of Nuclear Medicine, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 9Department of Medicine, University of Padova - Veneto Institute of Molecular Medicine, VIMM, Padova, PD, Italy; 10Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padova, PD, Italy†Anna Vittoria Lalinga passed away on January 26, 2020 and Luigi Del Vecchio passed away on August 16, 2018*These authors contributed equally to this workCorrespondence: Luciana ValvanoLaboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, ItalyTel +39 0972 726395Fax +39 0972 723509Email luciana.valvano@crob.itAbstract: Lymphoproliferative disorders are a heterogeneous

Published
2020

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

Author

Barilà, Gregorio, primary, Teramo, Antonella, additional, Calabretto, Giulia, additional, Vicenzetto, Cristina, additional, Gasparini, Vanessa Rebecca, additional, Pavan, Laura, additional, Leoncin, Matteo, additional, Vedovato, Susanna, additional, Frigo, Anna Chiara, additional, Facco, Monica, additional, Semenzato, Gianpietro, additional, and Zambello, Renato, additional

Published
2019
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25. Whole Exome Sequencing Analysis in Chronic Lymphoproliferative Disorder of NK Cells (CLPD-NK) Patients Fails to Detect Significant Viral Load

Author

Giussani, Edoardo, primary, Gasparini, Vanessa Rebecca, additional, Coppe, Alessandro, additional, Teramo, Antonella, additional, Binatti, Andrea, additional, Vicenzetto, Cristina, additional, Calabretto, Giulia, additional, Barilà, Gregorio, additional, Piazza, Francesco, additional, Semenzato, Gianpietro, additional, Bortoluzzi, Stefania, additional, and Zambello, Renato, additional

Published
2019
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26. Overexpression and Targeted Activation of the Protein Phosphatases SHP-1 Abrogates Survival Pathways in Large Granular Lymphocyte Leukemia (LGLL)

Author

Pagano, Mario Angelo, primary, Tibaldi, Elena, additional, Calabretto, Giulia, additional, Teramo, Antonella, additional, Dell'Amico, Luca, additional, Donà, Gabriella, additional, Barilà, Gregorio, additional, Vicenzetto, Cristina, additional, Gasparini, Vanessa Rebecca, additional, Trimarco, Valentina, additional, Facco, Monica, additional, Piazza, Francesco, additional, Semenzato, Gianpietro, additional, Brunati, Anna Maria, additional, and Zambello, Renato, additional

Published
2019
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27. High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia

Author

Andersson, Emma I., Tanahashi, Takahiro, Sekiguchi, Nodoka, Gasparini, Vanessa Rebecca, Bortoluzzi, Sabrina, Kawakami, Toru, Matsuda, Kazuyuki, Mitsui, Takeki, Eldfors, Samuli, Bortoluzzi, Stefania, Coppe, Alessandro, Binatti, Andrea, Lagström, Sonja, Ellonen, Pekka, Fukushima, Noriyasu, Nishina, Sayaka, Senoo, Noriko, Sakai, Hitoshi, Nakazawa, Hideyuki, Kwong, Yok-Lam, Loughran, Thomas P., Maciejewski, Jaroslaw P., Mustjoki, Satu, and Ishida, Fumihiro

Published
2016
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28. Insights into the Molecular Mechanism Accounting for Neutropenia in T-Large Granular Lymphocytes Leukemia

Author

Calabretto, Giulia, primary, Teramo, Antonella, additional, Mariotti, Barbara, additional, Rossato, Marzia, additional, Castellucci, Monica, additional, Barilà, Gregorio, additional, Leoncin, Matteo, additional, Vicenzetto, Cristina, additional, Gasparini, Vanessa Rebecca, additional, Facco, Monica, additional, Piazza, Francesco, additional, Semenzato, Gianpietro, additional, Bazzoni, Flavia, additional, and Zambello, Renato, additional

Published
2018
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29. High incidence of activating STAT5Bmutations in CD4-positive T-cell large granular lymphocyte leukemia

Author

Andersson, Emma I., Tanahashi, Takahiro, Sekiguchi, Nodoka, Gasparini, Vanessa Rebecca, Bortoluzzi, Sabrina, Kawakami, Toru, Matsuda, Kazuyuki, Mitsui, Takeki, Eldfors, Samuli, Bortoluzzi, Stefania, Coppe, Alessandro, Binatti, Andrea, Lagström, Sonja, Ellonen, Pekka, Fukushima, Noriyasu, Nishina, Sayaka, Senoo, Noriko, Sakai, Hitoshi, Nakazawa, Hideyuki, Kwong, Yok-Lam, Loughran, Thomas P., Maciejewski, Jaroslaw P., Mustjoki, Satu, and Ishida, Fumihiro

Published
2016
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30. Pro-inflammatory cells sustain leukemic clonal expansion in T-cell large granular lymphocyte leukemia.

Author

Vicenzetto C, Gasparini VR, Barila G, Teramo A, Calabretto G, Rampazzo E, Carraro S, Trimarco V, Trentin L, Facco M, Semenzato G, and Zambello R

Subjects
Humans, Killer Cells, Natural metabolism, Cytokines, Leukemia, Large Granular Lymphocytic genetics, Leukemia, Large Granular Lymphocytic pathology
Abstract

T-cell large granular lymphocyte leukemia (T-LGLL) is a chronic lymphoproliferative disorder characterized by the clonal expansion of T-cell large granular lymphocytes (T-LGL). Immunophenotypic and genotypic features contribute to discriminate symptomatic (CD8+ STAT3-mutated T-LGLL) from clinically indolent patients, this latter group including CD8+ wildtype (wt), CD4+ STAT5B-mutated and wt cases. T-LGL lymphoproliferation is sustained both by somatic gain-offunction mutations (i.e., STAT3 and STAT5B) and by pro-inflammatory cytokines, but little information is available on the activity of T-LGLL non-leukemic cells. In this study, we characterized pro-inflammatory cells in the peripheral blood of T-LGLL patients and analyzed their role in supporting the leukemic growth. In symptomatic patients we found that cell populations not belonging to the leukemic component showed a discrete pro-inflammatory pattern. In particular, CD8+ STAT3-mutated cases showed a skewed Th17/Treg ratio and an abnormal distribution of monocyte populations characterized by increased intermediate and non-classical monocytes. We also demonstrated that monocytes released high levels of interleukin-6 after CCL5 stimulation, a chemokine specifically expressed only by leukemic LGL. Conversely, in asymptomatic cases an altered distribution of monocyte populations was not detected. Moreover, T-LGLL patients' monocytes showed abnormal activation of signaling pathways, further supporting the different pathogenic role of monocytes in patients in discrete clinical settings. Altogether, our data contribute to deepening the knowledge on the different cell subtypes in T-LGLL, focusing particularly on non-leukemic cell populations and thus offering the rationale for new therapeutic strategies.

Published
2024
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