The raft marker GM1 identifies functional subsets of granular lymphocytes in patients with CD3+ lymphoproliferative disease of granular lymphocytes

Zambello, Renato; Cabrelle, Anna; Trentin, Livio; Agostini, Carlo; Semenzato, Gianpietro; Viola, Antonella

doi:10.1038/sj.leu.2403292

Cited by 5 publications

(7 citation statements)

References 31 publications

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“…The ganglioside GM1 is widely used as a marker for lipid rafts (25,26). In the present study, we analyzed the expression of GM1 in various non-Hodgkin's lymphomas.…”

Section: Introductionmentioning

confidence: 98%

GM1 Expression of Non-Hodgkin's Lymphoma Determines Susceptibility to Rituximab Treatment

Büschenfelde

Feuerstacke²,

Götze³

et al. 2008

Cancer Research

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Immunotherapy with rituximab alone or in conjunction with chemotherapy has significantly improved the treatment outcome of B-cell lymphoma patients. Nevertheless, a subpopulation of patients does not respond to rituximab. The reason for treatment failure as well as the exact mechanism of action is still uncertain. The function of rituximab has long been associated with the partitioning of CD20 molecules to lipid microdomains. We now show that the extent of CD20 recruitment to lipid rafts correlates with response to rituximab. In addition, expression of the raft-associated sphingolipid GM1 on lymphoma cells is associated with the susceptibility of lymphoma cells to rituximab. Furthermore, we show substantially different GM1 expression in various primary non-Hodgkin's lymphomas. Whereas chronic lymphocytic leukemia (CLL) cells have a low GM1 expression, marginal zone lymphoma cells exhibit much higher levels. Differences were not only detected among various lymphoma subgroups but also within one lymphoma subtype. Interestingly, whereas CLL cells from patients with high GM1 expression responded to rituximab, patients with low GM1 expressing CLL cells did not. These data show the importance of membrane microdomains in the effect of rituximab and may offer a predictive factor for the responsiveness of lymphoma cells to rituximab. [Cancer Res 2008;68(13):5414-22]

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“…The ganglioside GM1 is widely used as a marker for lipid rafts (25,26). In the present study, we analyzed the expression of GM1 in various non-Hodgkin's lymphomas.…”

Section: Introductionmentioning

confidence: 98%

GM1 Expression of Non-Hodgkin's Lymphoma Determines Susceptibility to Rituximab Treatment

Büschenfelde

Feuerstacke²,

Götze³

et al. 2008

Cancer Research

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“…Clonal LGLs constitutively express perforin, a component of the cytoplasmic granules found only in activated effector cytotoxic T-cells. As published by Zambello et al, the lipid raft molecule GM1 displayed distinctly bright expression patterns on subsets of granular lymphocytes from patients with clonal LGL expansion [32]. Constitutively bright expression of GM1 is consistent with prior in vivo antigen activation.…”

Section: Immunophenotypementioning

confidence: 55%

Large Granular Lymphocyte (LGL) Leukemia: Pathobiology, Diagnosis and Treatment

Ku¹,

Alekshun²,

Loughran³

et al. 2007

CCTR

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Clonal lymphoproliferative diseases of large granular lymphocytes (LGL) arise from both CD3-negative and CD3-positive cells, which define NK and T-LGL leukemia, respectively. Chronic neutropenia and anemia represent the most common clinical manifestation of these diseases but lymphocyte infiltration into bone marrow, spleen, and liver also occurs in some cases. The mechanism(s) responsible for expansion of the LGLs are unknown and the impact of lymphocytosis on the development of cytopenias is also incompletely defined. In this review, we discuss the incidence, clinical presentation, diagnostic criteria, and possible mechanisms of LGL leukemia pathogenesis. Despite the indolence of most cases of LGL leukemia, approximately 65% of patients will require therapy. There have been few controlled clinical trials conducted in this disease and long-term treatment is often required for sustained disease control. Novel therapies are primarily directed toward the targeted disruption of LGL leukemia survival. Conventional and novel therapeutics are discussed.

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“…Allo-HCT can create a microenvironment with abundant antigenic triggers for T-LGL clones to expand. 35–37 This is attested by the correlation of clinical events and longitudinal TRB gene repertoire analysis in a patient from our study who underwent allo-HSCT and developed clonally expanded T-LGL cells, gradually evolving into overt T-LGL leukemia. This highlights the thin line that segregates reactive T-LGL lymphoproliferations from their leukemic counterparts, while raising the question why the full blown T-LGL leukemia occurred so many years posttransplantation.…”

Section: Discussionmentioning

confidence: 66%

Context-dependent T-cell Receptor Gene Repertoire Profiles in Proliferations of T Large Granular Lymphocytes

et al. 2023

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T cell large granular lymphocyte (T-LGL) lymphoproliferations constitute a disease spectrum ranging from poly/oligo to monoclonal. Boundaries within this spectrum of proliferations are not well established. T-LGL lymphoproliferations co-occur with a wide variety of other diseases ranging from autoimmune disorders, solid tumors, hematological malignancies, post solid organ, and hematopoietic stem cell transplantation, and can therefore arise as a consequence of a wide variety of antigenic triggers. Persistence of a dominant malignant T-LGL clone is established through continuous STAT3 activation. Using next-generation sequencing, we profiled a cohort of 27 well-established patients with T-LGL lymphoproliferations, aiming to identify the subclonal architecture of the T-cell receptor beta (TRB) chain gene repertoire. Moreover, we searched for associations between TRB gene repertoire patterns and clinical manifestations, with the ultimate objective of discriminating between T-LGL lymphoproliferations developing in different clinical contexts and/or displaying distinct clinical presentation. Altogether, our data demonstrates that the TRB gene repertoire of patients with T-LGL lymphoproliferations is context-dependent, displaying distinct clonal architectures in different settings. Our results also highlight that there are monoclonal T-LGL cells with or without STAT3 mutations that cause symptoms such as neutropenia on one end of a spectrum and reactive oligoclonal T-LGL lymphoproliferations on the other. Longitudinal analysis revealed temporal clonal dynamics and showed that T-LGL cells might arise as an epiphenomenon when co-occurring with other malignancies, possibly reactive toward tumor antigens.

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The raft marker GM1 identifies functional subsets of granular lymphocytes in patients with CD3+ lymphoproliferative disease of granular lymphocytes

Cited by 5 publications

References 31 publications

GM1 Expression of Non-Hodgkin's Lymphoma Determines Susceptibility to Rituximab Treatment

GM1 Expression of Non-Hodgkin's Lymphoma Determines Susceptibility to Rituximab Treatment

Large Granular Lymphocyte (LGL) Leukemia: Pathobiology, Diagnosis and Treatment

Context-dependent T-cell Receptor Gene Repertoire Profiles in Proliferations of T Large Granular Lymphocytes

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