Citations 2
Tγδ LGLL identifies a subset with more symptomatic disease: analysis of an international cohort of 137 patients
Barilà, Gregorio , Grassi, Angela , Cheon, HeeJin , Calabretto, Giulia , Chahal, Jasmanet , Vicenzetto, Cristina , Almeida, Júlia , Shemo, Bryna C. , Muñoz‐García, Noemí , Pastoret, Cédric , Oshimi, Kazuo, Sokol, Lubomir, Ishida, Fumihiro , Lamy, Thierry , Morice, William G. , Loughran, Thomas P. , Teramo, Antonella , Chahal, Jasmanet , Vicenzetto, Cristina , Almeida, Julia , Munoz-Garcia, Noemi , Nakazawa, Hideyuki , Morice, William George , Semenzato, Gianpietro , Shi, Min , Gasparini, Vanessa Rebecca , Órfão, Alberto , Zambello, Renato
Blood | September 12, 2022 | Volume: 141 | Issue: 9 | Pages: 1036-1046
Abstract Tγδ large granular lymphocyte leukemia (LGLL) is a rare variant of T-cell LGLL (T-LGLL) that has been less investigated as compared with the more frequent Tαβ LGLL, particularly in terms of frequency of STAT3 and STAT5b mutations. In this study, we characterized the clinical and biological features of 137 patients affected by Tγδ LGLL; data were retrospectively collected from 1997 to 2020 at 8 referral centers. Neutropenia and anemia were the most relevant clinical features, being present in 54.2% and 49.6% of cases, respectively, including severe neutropenia and anemia in ∼20% of cases each. Among the various treatments, cyclosporine A was shown to provide the best response rates. DNA samples of 97 and 94 cases were available for STAT3 and STAT5b mutation analysis, with 38.1% and 4.2% of cases being mutated, respectively. Clinical and biological features of our series of Tγδ cases were also compared with a recently published Tαβ cohort including 129 cases. Though no differences in STAT3 and STAT5b mutational frequency were found, Tγδ cases more frequently presented with neutropenia (P = .0161), anemia (P < .0001), severe anemia (P = .0065), and thrombocytopenia (P = .0187). Moreover, Vδ2− cases displayed higher frequency of symptomatic disease. Overall, Tγδ cases displayed reduced survival with respect to Tαβ cases (P = .0017). Although there was no difference in STAT3 mutation frequency, our results showed that Tγδ LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared with Tαβ LGLL.
Genomic profiling for clinical decision making in lymphoid neoplasms
Leval, Laurence de , Alizadeh, Ash A. , Bergsagel, P. Leif , Campo, Elı́as , Davies, Andrew , Doǧan, Ahmet , Fitzgibbon, Jude , Horwitz, Steven M. , Melnick, Ari , Morice, William G. , Nadel, Bertrand , Rosenquist, Richard , Rossi, Davide , Advani, Ranjana H. , Allen, Carl E. , Ansell, Stephen M. , Chan, Wing C. , Cook, James R. , Cook, Lucy , d’Amore, Francesco, Dirnhofer, Stefan , Dreyling, Martin , Dunleavy, Kieron , Hodson, Daniel J. , Klapper, Wolfram , Kim, Won Seog , King, Rebecca L. , Ko, Young Hyeh , LaCasce, Ann S. , Lenz, Georg , Pasqualucci, Laura , Rosenwald, Andreas , Miguel, Jesús F. San , Staudt, Louis M. , Weigert, Oliver , Wilson, Wyndham H. , Wu, Catherine J. , Bagg, Adam , Dirnhofer, S , Bergsagel, P. Leif , de Leval, Laurence , Melnick, Ari , Morin, Ryan D , Nadel, Bertrand , Pileri, Stefano , Rosenquist, Richard , Salaverria, Itziar , Steidl, Christian , Treon, Steven , Zelenetz, Andrew D , Allen, Carl E , Ansell, Stephen M , Chan, Wing C , Cook, James R , Cook, Lucy B , d'Amore, Francesco , Dreyling, Martin , Dunleavy, Kieron , Feldman, Andrew L , Fend, Falko , Gaulard, Philippe , Ghia, Paolo , Gribben, John G. , Hermine, Olivier , Hodson, Daniel J , Hsi, Eric D , Inghirami, Giorgio , Jaffe, Elaine S , Karube, Kennosuke , Kataoka, Keisuke , Klapper, Wolfram , King, Rebecca L , Hyeh, Young , LaCasce, Ann Steward , Lenz, Georg , Piris, Miguel , Pittaluga, Stefania , Pasqualucci, Laura , Quintanilla-Martinez, Leticia , Rodig, Scott J , Rosenwald, Andreas , Salles, Gilles A , San-Miguel, Jesus , Savage, Kerry J , Sehn, Laurie H , Semenzato, Gianpietro , Staudt, Louis M , Swerdlow, Steven H , Tam, Constantine S , Trotman, Judith , Vose, Julie , Weigert, Oliver , Wilson, Wyndham H , Winter, Jane N , Wu, Catherine J , Zinzani, Pier Luigi , Zucca, Emanuele , Bagg, Adam , Scott, David W , Morice, William George , Campo, Elías , Advani, Ranjana H , Dogan, Ahmet , Davies, Andrew , Fitzgibbon, Jude , Horwitz, Steven M , Alizadeh, Ash A , Pileri, Stefano , Salaverría, Itziar , Steidl, Christian , Treon, Steven P. , Zelenetz, Andrew D. , Feldman, Andrew L. , Ghia, Paolo , Hermine, Olivier , Hsi, Eric D. , Inghirami, Giorgio , Jaffe, Elaine S. , Karube, Kennosuke , Martin-Subero, Jose Ignacio , Piris, Miguel Á. , Pittaluga, Stefania , Quintanilla‐Martínez, Leticia , Salles, Gilles , Savage, Kerry J. , Sehn, Laurie H. , Swerdlow, Steven H. , Tam, Constantine S. , Vose, Julie M. , Winter, Jane N. , Zinzani, Pier Luigi , Zucca, Emanuele , Scott, David W.
Blood | August 24, 2022 | Volume: 140 | Issue: 21 | Pages: 2193-2227
Abstract With the introduction of large-scale molecular profiling methods and high-throughput sequencing technologies, the genomic features of most lymphoid neoplasms have been characterized at an unprecedented scale. Although the principles for the classification and diagnosis of these disorders, founded on a multidimensional definition of disease entities, have been consolidated over the past 25 years, novel genomic data have markedly enhanced our understanding of lymphomagenesis and enriched the description of disease entities at the molecular level. Yet, the current diagnosis of lymphoid tumors is largely based on morphological assessment and immunophenotyping, with only few entities being defined by genomic criteria. This paper, which accompanies the International Consensus Classification of mature lymphoid neoplasms, will address how established assays and newly developed technologies for molecular testing already complement clinical diagnoses and provide a novel lens on disease classification. More specifically, their contributions to diagnosis refinement, risk stratification, and therapy prediction will be considered for the main categories of lymphoid neoplasms. The potential of whole-genome sequencing, circulating tumor DNA analyses, single-cell analyses, and epigenetic profiling will be discussed because these will likely become important future tools for implementing precision medicine approaches in clinical decision making for patients with lymphoid malignancies.