Expression of Vβ Gene Segments by Sezary Cells

Gorochov, Guy; Bachelez, Hervé; Cayuela, Jean Michel; Legac, Éric; Laroche, Liliane; Dubertret, Louis; Sigaux, François

doi:10.1111/1523-1747.ep12312560

Cited by 39 publications

(39 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…14,15 The diagnosis of SS relies on the circulating Sézary cell count, as determined by cytomorphology, and T-cell clonality, as determined by molecular approaches. 16,[22][23][24][25] However, the malignancy to T-cell clones has never been determined in patients with SS, and it is unknown whether molecular studies would detect nonmalignant expanded populations.…”

Section: Discussionmentioning

confidence: 99%

“…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, however, is limited by the lack of available mAbs reacting with some TCR VDJ␤ gene products in the blood 4,16,17,19,20 and in skin samples. 21 Moreover, there is no clear-cut limit of percentage of TCR V␤ expansion associated with malignancy.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, identifying T-cell clones in patients with SS relies on molecular analysis of the TCR␤ or TCR␥ chains at the DNA and RNA levels. Various polymerase chain reaction (PCR)-based techniques-including PCR-␤, 16 PCR-␥, 22 PCR-denaturing gradient gel electrophoresis-␥ (PCR-DGGE-␥ ), 23 PCR-polyacrylamide gel electrophoresis-␥ (PCR-PAGE-␥), 24 and PCR-single-strand conformation polymorphism-␥ (PCR-SSCP-␥) 25 -have been validated. Immunoscopy based on TCR V␤ mRNA spectratype analysis and sequencing of the CDR3 region is a sensitive technique that has been applied for the detection and monitoring of T-cell clones in different conditions, including SS.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Significance of circulating T-cell clones in Sézary syndrome

Ortonne

Huet

Gaudez

et al. 2006

Blood

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Significance of circulating T-cell clones in Sézary syndrome

Ortonne

Huet

Gaudez

et al. 2006

Blood

View full text Add to dashboard Cite

show abstract

“…Patients selected to enter the present study exhibited a Sézary cell ratio exceeding 5% of PBLs (range, 5-51; median, 14.5; Table 1). The quantitative evaluation of peripheral blood tumor cells was assessed by combining CD4/anti-TCRVh double immunostaining flow cytometric analysis of PBLs and TCRVh complementary-determining region 3 length analysis by the immunoscope method as previously detailed (21). Human PBLs from normal healthy plasma donors were obtained through the ''Etablissement Français du Sang'' (Hô pital Saint-Louis, Paris, France).…”

Section: Patientsmentioning

confidence: 99%

Inhibition of IκB Kinase Subunit 2 in Cutaneous T-Cell Lymphoma Down-Regulates Nuclear Factor-κB Constitutive Activation, Induces Cell Death, and Potentiates the Apoptotic Response to Antineoplastic Chemotherapeutic Agents

Sors

Jean-Louis

Bégué

et al. 2008

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: A key molecular feature of cutaneous T-cell lymphomas (CTCL) is the constitutive activation of the nuclear factor-nB (NF-nB) transcription factor. We investigated in vitro the effects on CTCL survival and chemoresistance of a specific inhibition of InB kinase subunit 2 (IKK2). Experimental Design: Selective IKK2 inhibition was carried out by transfection of SeAx and MyLa CTCL lines with an inactive form of IKK2 and by exposing these lines and tumor cells from 10 patients with Se¤ zary syndrome (SS) to AS602868, a new IKK2 inhibitor. The constitutive nuclear translocation of NF-nB was analyzed by electrophoretic mobility shift assay and confocal microscopy. Apoptosis was determined by Annexin V/propidium iodide^positive staining and mitochondrial transmembrane potential alterations as well as poly(ADP-ribose)polymerase cleavage. The expression of Bcl-2 family oncoproteins and survivin was studied by immunoblotting. Results: Specific IKK2 inhibition resulting from transfection or from incubation with AS602868 allowed a down-regulation of NF-nB transcriptional activity. As shown by electrophoretic mobility shift assay and apoptosis assays, AS602868 down-regulated the nuclear translocation of NF-nB and induced a potent apoptotic response in CTCL lines and in tumor cells from patients with SS while preserving the viability of both peripheral blood lymphocytes from healthy donors and of nonmalignant T cells from SS patients. Moreover, CTCL death induction by conventional antineoplastic agents etoposide and vincristine was potentiated by AS602868. Finally, AS602868-induced apoptosis of CTCL cells was associated with an up-regulation of Bax dimers and a decrease of survivin. Conclusion: These results indicate that IKK2 inhibition represents a promising strategy for the treatment of advanced stages of CTCL.

show abstract

“…Jedoch lassen sich weder morphologische [40], immunphänotypische [41 ± 43], ultrastrukturelle [44,45] Merkmale finden, die zuverlässig diese wichtige Unterscheidung ermöglichen. Hier erbrachte auch die Analyse der Vb-Genexpression der T-Zell-Rezeptoren auf Proteinebene [46,47] sowie der Nachweis chromosomaler Aberrationen [48,49] bisher keine für die Routine praktischen Fortschritte.…”

Section: Bedeutung Der Klonalität In Der Ausbreitungsdiagnostikunclassified

Diagnostischer Stellenwert und klinische Bedeutung der Analyse von T-Zellrezeptor-Genumlagerungen beim kutanen T-Zell-Lymphom

Assaf¹

2004

Akt Dermatol

View full text Add to dashboard Cite

ZusammenfassungKutane T-Zell-Lymphome (CTCL) stellen eine Gruppe lymphoproliferativer Hauterkrankungen dar, die durch klonale Akkumulation von T-Lymphozyten-Populationen charakterisiert sind. Die Diagnose wird in der Regel aufgrund klinischer und histologischer charakteristischer Eigenschaften der CTCL gestellt. Schwierigkeiten bereitet die Diagnosestellung insbesondere in frühen Stadien, aber auch in seltenen Varianten der CTCL. In diesen Fällen ist der Nachweis klonaler T-Zell-Populationen durch identisch umgelagerte T-Zellrezeptor-Gene eine wertvolle Hilfe. So zeigen PCR-basierende Techniken zum Nachweis klonaler T-Zell-Populationen eine hohe Sensitivität von 70 ± 90 % in Hautbiopsien früher CTCL-Stadien. Nach Diagnosestellung ist der nächste wichtige Schritt die Ausbreitungsdiagnostik des CTCL, sinkt doch die Überlebensrate drastisch bei Auftreten extrakutaner Manifestationen wie z.B. bei Infiltration der Lymphknoten oder viszeraler Organe. Ein Stadienwechsel, d.h. die Progression der Erkrankung, wird in der Regel klinisch erst spät entdeckt. Insbesondere der Lymphknotenbefall, der erfahrungsgemäû als erste extrakutane Manifestation des CTCL gilt, stellt sowohl den Kliniker als auch den Histologen vor diagnostische Probleme. Hier konnten wir in einer aktuellen Studien zeigen, dass in ca. 50 % der dermatopathischen Lymphknoten identische klonale T-ZellPopulationen wie in den CTCL-Läsionen der Haut nachweisbar sind. Des Weiteren zeigte sich, dass diese Patienten eine reduzierte Überlebensrate haben, ähnlich denen, die eine histologisch manifeste Lymphknoteninfiltration durch das CTCL haben. Diese Daten belegen, dass T-Zellrezeptor-Umlagerungsanalysen bei Patienten mit CTCL sowohl eine diagnostische als auch prognostische Bedeutung haben und somit ein akkurates Staging ermöglichen. AbstractCutaneous T-cell lymphoma (CTCL) is a clonal lymphoproliferative malignancy primarily involving the skin. Routine diagnosis of CTCL is based on its characteristic clinical and histopathologic features. However, the broad clinical and histological spectrum of the disease, especially of its early stages and rare variants, often complicates the differentiation between malignant CTCL and benign lymphoproliferative or reactive skin diseases. In these cases demonstration of a clonal T-cell population by detection of identically rearranged T-cell receptor genes (TCR) provides an adjunct. Using this approach clonality could be demonstrated in 70-90 % in CTCL biopsies of early stages by recent PCR-based studies, indicating a high sensitivity. After achieving the correct diagnosis the next important step is to stage the disease in CTCLpatients. Patients with CTCL usually have an indolent course with a 5-year survival of approximately 87%. However, in a significant number of patients the disease may progress and disseminated extracutaneous manifestations may develop involving the lymph nodes, blood and visceral organs. The prognosis for patients with widespread manifestation of CTCL beyond the skin is poor. Therefore, accurate evaluatio...

show abstract

Expression of Vβ Gene Segments by Sezary Cells

Cited by 39 publications

References 28 publications

Significance of circulating T-cell clones in Sézary syndrome

Significance of circulating T-cell clones in Sézary syndrome

Inhibition of IκB Kinase Subunit 2 in Cutaneous T-Cell Lymphoma Down-Regulates Nuclear Factor-κB Constitutive Activation, Induces Cell Death, and Potentiates the Apoptotic Response to Antineoplastic Chemotherapeutic Agents

Diagnostischer Stellenwert und klinische Bedeutung der Analyse von T-Zellrezeptor-Genumlagerungen beim kutanen T-Zell-Lymphom

Contact Info

Product

Resources

About