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Biologie des multiplen Myeloms

Biology of multiple myeloma

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Zusammenfassung

Die molekulare Pathogenese des Multiplen Myeloms ist als mehrstufiger Prozess anzusehen, für den sowohl die komplexen genetischen Veränderungen der Myelomzellen als auch die Eigenschaften der Knochenmarkstromazellen verantwortlich sind. Zu den frühesten chromosomalen Ereignissen zählen Translokationen des Immunglobulinschwerketten-Gens, wodurch Onkogene der Translokationspartner-Region (z.B. cyclin D1 auf 11q13 oder fgfr3/mmset auf 4p16.3) dysreguliert werden, und Deletionen von Chromosom 13q, wo ein kritisches Tumorsuppressorgen vermutet wird. Die Proliferation und das Überleben der Myelomzellen wird von den Knochenmarkstromazellen durch Zytokine unterstützt. Osteoklasten aktivierende Faktoren wie MIP1α sowie ein Ungleichgewicht im RANKL/Osteoprotegerin-System bilden die Basis der osteolytischen Knochenveränderungen beim multiplen Myelom. Es ist zu erwarten, dass die weitere Charakterisierung dieser biologischen Grundlagen zur Identifizierung molekularer Targets führt, welche für neue Therapieansätze genützt werden können.

Abstract

For our understanding of multiple myeloma, features of the malignant clone and changes induced by the bone marrow microenvironment are equally important. Among the earliest genetic events are translocations of the immunoglobulin heavy chain gene locus, which lead to dysregulation of oncogenes at translocation partner regions (e.g., cyclin D1 at 11q13 or fgfr3/mmset at 4p16.3) and deletions of chromosome 13q, the site of a putative tumor suppressor gene. Bone marrow stromal cells support growth and survival of myeloma cells via various cytokines. Osteoclast-activating factors such as MIP1α as well as imbalances in the RANKL/osteoprotegerin system represent the molecular basis for myeloma bone disease. Further characterization of critical events in the development of monoclonal gammopathies will likely lead to the identification of new molecular targets for future therapeutic interventions.

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  1. Klinische Abt. für Onkologie, Klinik für innere Medizin, Medizinische Universität Wien

    J. Drach

  2. Klinische Abt. für Onkologie, Klinik für innere Medizin, Medizinische Universität Wien, Währinger Gürtel 18–20, 1090 , Wien

    J. Drach

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Drach, J. Biologie des multiplen Myeloms. Onkologe 10, 801–808 (2004). https://doi.org/10.1007/s00761-004-0750-z

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  • DOI: https://doi.org/10.1007/s00761-004-0750-z

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