Expression of Cytotoxic Proteins by Neoplastic T Cells in Mycosis Fungoides Increases with Progression from Plaque Stage to Tumor Stage Disease

Vermeer, Maarten H.; Geelen, Françoise A. M. J.; Kummer, J. Alain; Meijer, Chris J.L.M.; Willemze, Rein

doi:10.1016/s0002-9440(10)65372-2

Cited by 82 publications

(39 citation statements)

References 37 publications

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“…Of interest, most CD4 ϩ cutaneous T-cell lymphomas have a mature ␣␤ memory T-cell phenotype, 24 consistent with our own results. Contrary to a recent report by Vermeer et al, 25 we did not find a correlation between disease stage and CtxP expression. The lower percentage of CtxP ϩ cases in our study (6% vs 45%), and the lack of correlation between CtxP ϩ and disease stage may be due to our more stringent positive inclusion criterion (20% vs 10%), and/or our small number of tumor stage cases.…”

Section: Gm ؊ Ctxp ؉ Lymphomas (Pc-alcls S-alcls Sptcls)contrasting

confidence: 99%

The serine protease granzyme M is preferentially expressed in NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity

Krenács

Smyth²,

Bagdi

et al. 2002

Blood

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Section: Gm ؊ Ctxp ؉ Lymphomas (Pc-alcls S-alcls Sptcls)contrasting

confidence: 99%

The serine protease granzyme M is preferentially expressed in NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity

Krenács

Smyth²,

Bagdi

et al. 2002

Blood

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“…The finding of expanded nonmalignant T-cell clones in the blood of SS patients is not an unexpected finding. Cytotoxic T-cell populations indeed can be found in the skin and in the blood of patients with CTCL, [34][35][36][37] and their ability to react specifically to tumor cells has been shown. 37 Whether expanded nonmalignant T-cell clones in SS are mostly antitumor cytotoxic expanded T-cell clones is a tempting hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Significance of circulating T-cell clones in Sézary syndrome

Ortonne

Huet

Gaudez

et al. 2006

Blood

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Identification of malignant Sé zary cells by T-cell receptor (TCR) clonality studies is routinely used for the diagnosis of Sé zary syndrome, but T-cell clones expressed in a single patient have never been accurately characterized. We previously reported that CD158k expression delineates Sé zary syndrome malignant cells, and, more recently, we identified vimentin at the surface membranes of Sé zary cells and normal activated lymphocytes. In the present study, T-cell clones from 13 patients with Sé zary syndrome were identified by immunoscopy and further characterized in the blood according to their TCR V␤, CD158k, and vimentin cell-surface expression. We found in most patients a unique malignant T-cell clone that coexpressed CD158k and vimentin and that, when patients were tested, was also present in the skin. However, in some patients we detected the presence of a nonmalignant circulating clone expressing high amounts of vimentin and lacking IntroductionSézary syndrome (SS) is an erythrodermic, aggressive, cutaneous T-cell lymphoma characterized by a malignant T-cell clone that localizes in the blood and skin. In the absence of a specific marker for malignant Sézary cells, a diagnosis of SS relies on the circulating Sézary cell count and on the molecular detection of a circulating T-cell clone. Given that the cytomorphology of Sézary cells is not specific to SS, 1,2 identification of a specific marker of malignant Sézary cells has been a challenging issue. Besides a T-cell memory phenotype, CD4 ϩ CD45RO ϩ , Sézary cells were shown to lack CD26 3-5 and to have diminished CD3 expression, 6 whereas the loss of CD7 3,7 appears not to be a specific feature of the malignant T-cell clone. 5,8 More recently, it has been shown that Sézary cells specifically overexpress T-plastin, which, however, cannot be used as a cell-surface marker because it is located in the cytoskeleton, in association with actin. 9 New markers of Sézary cells were described, including KIR3DL2/CD158k, the first positive cell-surface marker of Sézary cells. In patients with SS, KIR3DL2/CD158k is dimly expressed by circulating and cutaneous CD4 ϩ lymphocytes. [10][11][12] In healthy persons, CD158k is absent in CD4 ϩ lymphocytes, and only minor subsets of T CD8 ϩ and natural killer (NK) lymphocytes express high amount of this antigen. 13 SC5 monoclonal antibody (mAb) was shown to react with an unknown cell-surface antigen expressed by normal activated lymphocytes and Sézary cells, whereas it failed to stain most circulating T lymphocytes in healthy individuals. 14 We found that SC5 mAb specifically recognizes vimentin (VIM) at the cell surface of viable activated T lymphocytes and is effectively expressed by Sézary cells. 15 The finding of an expanded T-cell clone in the blood of patients with SS is commonly considered to be a diagnostic marker. TCR V␤ phenotyping with specific mAbs may identify a "clonotypic" lymphocyte subset as an expanded population bearing a single TCR V␤ chain, which may be of diagnostic value. 3,[16][17][18] This approach, h...

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“…54 Expression of cytotoxic proteins (T-cell intracellular antigen-1 [TIA-1], granzyme B) by the neoplastic CD4 ϩ T-cells has been detected in 10% of MF plaques, but is much more common in tumors showing blastic transformation. 56 Genetic features. Clonal T-cell receptor gene rearrangements are detected in most cases.…”

Section: Mycosis Fungoidesmentioning

confidence: 99%