Diagnosis of cutaneous T cell lymphoma by use of monoclonal antibodies reactive with tumor-associated antigens.

Berger, Carole L.; Morrison, Sherie L.; Chu, Anthony; Patterson, Jennifer; Estabrook, Alison; Takezaki, Shinichero; Sharon, Jacqueline; Warburton, Dorothy; Irigoyen, Oscar H.; Edelson, Richard L.

doi:10.1172/jci110719

Cited by 75 publications

(16 citation statements)

References 27 publications

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“…[1][2][3][4][5] A high percentment results in Zap70 activation after its binding to the tyrosylage of the malignant cells constitutively express BE2, a late phosphorylated immunoreceptor tyrosine-based activation activation marker of 78 kDa, that appears on cloned normal motifs (ITAMs) of the chains and the CD3 complex 23,24 (for T cells only after stimulation with specific antigen, and on review see Ref. 25) and in rapid tyrosine phosphorylation and freshly isolated normal T cells in response to mitogens, 6,7 sugactivation of Syk. 26 The signaling initiated by TCR activation gesting that CTCL cells have been activated by their surroundis transmitted from the cell membrane through the cytoplasm ing dermal environment.…”

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confidence: 99%

Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk

Fargnoli

Berger

et al. 1997

Leukemia

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18). In addition, TCR engagecharacteristic of 'memory' T lymphocytes. 1-5 A high percentment results in Zap70 activation after its binding to the tyrosylage of the malignant cells constitutively express BE2, a late phosphorylated immunoreceptor tyrosine-based activation activation marker of 78 kDa, that appears on cloned normal motifs (ITAMs) of the chains and the CD3 complex 23,24 (for T cells only after stimulation with specific antigen, and on review see Ref. 25) and in rapid tyrosine phosphorylation and freshly isolated normal T cells in response to mitogens, 6,7 sugactivation of Syk. 26 The signaling initiated by TCR activation gesting that CTCL cells have been activated by their surroundis transmitted from the cell membrane through the cytoplasm ing dermal environment. Since CTCL lymphocytes can proto the nucleus and induces quiescent T cells to undergo cell liferate in the cutaneous compartment but are extremely division and maturation, processes critical for clonal expandifficult to cultivate in vitro, their neoplastic growth appears sion and initiation of the immune responses. to reflect in vivo stimulation, possibly through their TCR, orWe selected for investigation several immediate key reacantigen-independent pathways or cytokines. IL-7 might be one tions essential for T cell receptor-mediated signal transducof the required growth factors for CTCL cells in the skin since tion, proliferation and effector functions. Our results, based transgenic mice constitutively producing IL-7 developed on analysis of a limited sample of CTCL cells (from four extensive dermal infiltration followed by dermotropic lympatients), show nevertheless, common characteristics, ie phoma. 8,9 However, although IL-7 is produced by keradeficiencies in critical immediate functions associated with tinocytes, it is a weak in vitro CTCL mitogen, 10 and purified TCR activation. These include molecules participating in populations of CTCL cells were sustained in culture for only events proximal and distal to the TCR such as: (1) reduced a short period (such as a week) by mixtures of cytokines that levels of basal and stimulated tyrosyl-phosphorylated proteins include IL-7 and IL-2. 11,12 belonging to a wide range of signaling molecules; The preferential expression of CD45RO and the clonal TCR (2) suppressed specific activity of membrane-bound Csk and rearrangement suggest that CTCL clones have encountered a Lck; (3) failure to activate membrane-bound PTPase; (4) failure to activate Zap70 and to induce its association with the TCR chain; and (5) reduced expression and activity of Syk. LimitedCorrespondence: R Halaban, Department of Dermatology, Yale Unicomparative analysis with the CD4 + /CD45RO + subpopulation

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confidence: 99%

Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk

Fargnoli

Berger

et al. 1997

Leukemia

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“…The monoclonal antibody (MAb) reactive with BE2-78 (Berger et al, 1982) was derived through immunization of mice with lymphocytes from a patient with HTLV-1 1 , adult T-cell leukemia (ATL). It recognizes a 78-kDa single-chain membrane protein on malignant T cells of patients with cutaneous T-cell lymphoma (CTCL), and ATL, on Epstein-Barr virus (EBV)-infected B cells, on B-cell chronic lymphocytic leukemia lymphocytes and on some lymphocytes from patients with acquired immunodeficiency syndrome (Berger et al, 1986).…”

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A lymphocyte cell surface heat shock protein homologous to the endoplasmic reticulum chaperone, immunoglobulin heavy chain binding protein BIP

et al. 1997

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BE2 is a cell surface monomeric 78-kDa protein (BE2-78) expressed on the malignant lymphocytes of cutaneous T-cell lymphoma and adult T-cell leukemia, on some lymphocytes from patients with acquired immunodeficiency syndrome and on Epstein-Barr virus-transformed B cells. BE2-78 positivity of cutaneous T-cell lymphoma tumor cells is a useful diagnostic and prognostic determinant in evaluating patients with that disorder. The BE2-78 protein was isolated from Epstein Barr virus-transformed B cells, purified by 1-and 2-dimensional electrophoresis and then sequenced. The sequence of 4 isolated peptide fragments was highly homologous with the 78-kDa heat shock protein, BiP, an endoplasmic reticulum chaperone. The similarity between BiP and BE2-78 was supported by the demonstration that BE2-78, like BiP, avidly binds to ATP. However, polyclonal and monoclonal reagents that recognize cytoplasmic 70-and 78-kDa heat shock proteins do not detect the BE2-78 antigen on the cell surface of cutaneous T-cell lymphoma or Epstein Barr virustransformed lymphocytes, and peptide mapping demonstrates sequence divergence, suggesting that either they are distinct or conformationally different molecules. Our results indicate that BE2-78 is a cell surface heat shock protein. The possibility that malignant or transformed lymphocytes may express cell surface molecules with the capacity to bind a spectrum of exogenous or endogenous peptides has potential implications for tumor immunology. Int.

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“…Both tissue sections and cell suspensions, either fresh, or from cultured cell lines, may be studied by this method. Berger et al (1982), using an indirect imtnunofluorcscent technique, have demonstrated circulating neoplastic T cells, reactive with monoclonal antibodies BEl and BE2 in patients with cutaneous T-cell lymphoma which, clinically, appears to be confined to the skin. These monoclonals were made against the leukemic helper T cells of a patient with cutaneous T-cell lymphotna.…”

Section: Applications Of the Immunofluorescent Techniquesmentioning

confidence: 99%

Immunofluorescence techniques in dermatopathology

Patterson

1983

J Cutan Pathol

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Diagnosis of cutaneous T cell lymphoma by use of monoclonal antibodies reactive with tumor-associated antigens.

Cited by 75 publications

References 27 publications

Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk

Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk

A lymphocyte cell surface heat shock protein homologous to the endoplasmic reticulum chaperone, immunoglobulin heavy chain binding protein BIP

Immunofluorescence techniques in dermatopathology

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