The candidate immunotherapeutical target, the receptor for hyaluronic acid-mediated motility, is associated with proliferation and shows prognostic value in B-cell chronic lymphocytic leukemia.

Giannopoulos, K; Mertens, D; Bühler, A; Barth, T F E; Idler, I; Möller, P; Kröber, A; Greiner, J; Chocholska, S; Dmoszyñska, A; Roliñski, J; Döhner, H; Stilgenbauer, S; Schmitt, M

Giannopoulos, K; Mertens, D; Bühler, A; Barth, T F E; Idler, I; Möller, P; Kröber, A; Greiner, J; Chocholska, S; Dmoszyñska, A; Roliñski, J; Döhner, H; Stilgenbauer, S; Schmitt, M.

Afiliación

Giannopoulos K; Department of Internal Medicine III, University of Ulm, Ulm, Germany. giannop@tlen.pl

Leukemia ; 23(3): 519-27, 2009 Mar.

Article en En | MEDLINE | ID: mdl-19092852

RESUMEN

Differential expression of molecules in chronic lymphocytic leukemia (CLL) may define prognostic markers and suitable targets for immunotherapy. Expression of the tumor-associated antigen (TAA) RHAMM (receptor for hyaluronic acid-mediated motility) as well as RHAMM splicing variants was assessed in series of 72 CLL patients. Quantitative reverse transcriptase PCR showed higher RHAMM expression in high-risk CLL patients, as well as in the advanced stages of the disease. CLL cases with a higher RHAMM expression showed a significantly shorter median treatment-free survival. Among patients with mutated immunoglobulin heavy chain genes, an analysis of RHAMM expression enabled to distinguish subgroup of patients with favorable prognosis. In lymph nodes, RHAMM staining correlated with a higher Ki-67 index and CD40L expression. Functionally, stimulation with CD40L enhanced RHAMM expression in CLL. We further characterized RHAMM-specific CD8(+) T cells in patients with CLL, as the expression of TAAs might influence the clinical outcome by the means of immune reactions. The cytotoxic potential of RHAMM-specific T cells was shown against target cells bearing RHAMM-derived epitope as well as against CLL cells expressing RHAMM. In conclusion, RHAMM expression appears to be of prognostic value, as well as may reflect the proliferative capacity of CLL cells, and might therefore represent interesting target for immunotherapy.

Asunto(s)

Proteínas de la Matriz Extracelular/fisiología; Receptores de Hialuranos/fisiología; Leucemia Linfocítica Crónica de Células B/metabolismo; Proteínas de Neoplasias/fisiología; Adulto; Anciano; Anciano de 80 o más Años; Ligando de CD40/análisis; Ligando de CD40/farmacología; Linfocitos T CD8-positivos/inmunología; Linfocitos T CD8-positivos/patología; División Celular; Citotoxicidad Inmunológica; Progresión de la Enfermedad; Supervivencia sin Enfermedad; Proteínas de la Matriz Extracelular/análisis; Femenino; Humanos; Receptores de Hialuranos/análisis; Cadenas Pesadas de Inmunoglobulina/genética; Leucemia Linfocítica Crónica de Células B/genética; Leucemia Linfocítica Crónica de Células B/mortalidad; Leucemia Linfocítica Crónica de Células B/patología; Masculino; Persona de Mediana Edad; Proteínas de Neoplasias/análisis; Pronóstico; Isoformas de Proteínas/análisis; Isoformas de Proteínas/fisiología; Empalme del ARN; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Proteínas de la Matriz Extracelular / Receptores de Hialuranos / Proteínas de Neoplasias Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2009 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

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