Zusammenfassung
Hintergrund
Das Multiple Myelom (MM) ist eine hämatologische Neoplasie, bei der sich maligne Plasmazellen im Knochenmark (KM) ausbreiten, die gesunde Hämatopoese verdrängen und lytische Knochenläsionen verursachen. Trotz erheblicher Erfolge in der Therapie ist bei den meisten Patienten eine Krankheitsprogression nicht zu verhindern. Das MM gilt weiterhin als unheilbar.
Ziel der Arbeit
Die Progressionsphasen werden beschrieben, um in diesem Rahmen die aktuellen Erkenntnisse zur Pathogenese des MM vorzustellen.
Material und Methoden
Diskussion von Grundlagenarbeiten und aktuellen wissenschaftlichen Publikationen.
Ergebnisse
Genetische Prädisposition, Inflammation und abnorme Immunantwort sind an der Genese des MM beteiligt. Das initiierende genomische Ereignis erfolgt während der B‑Zell-Reifung, woraufhin monoklonale Plasmazellen das KM besiedeln. Dieses frühe Stadium wird als monoklonale Gammopathie unklarer Signifikanz bezeichnet. Ab einer KM-Infiltration >10 % liegt ein asymptomatisches Myelom vor. Treten Endorganschädigungen auf, besteht ein symptomatisches, behandlungsbedürftiges MM. Nach neuesten Erkenntnissen ist das MM durch eine räumliche klonale Heterogenität gekennzeichnet, wobei aggressive Klone auf fokale Läsionen begrenzt und somit am Beckenkamm nicht nachweisbar sein können. Aggressive Klone haben oft vollständig inaktivierte Tumorsuppressorgene, wie TP53, und werden durch die Therapie selektiert, weshalb jedes Rezidiv beim MM schwieriger zu behandeln ist.
Diskussion
Die Tumorbiologie bestimmt den Verlauf des MM und erklärt die heterogenen Therapieergebnisse, die trotz intensiver Behandlung zu beobachten sind.
Abstract
Background
Multiple myeloma (MM) is a hematologic malignancy characterized by monoclonal plasma cells infiltrating the bone marrow thereby causing anemia and lytic bone lesions. Despite significant improvement in overall survival, most MM patients inevitably, yet unpredictably, develop refractory disease and MM remains largely incurable.
Objective
This article describes the stages of progression and presents current insights into the pathogenesis of MM.
Material and methods
Discussion of basic conceptional works and most recent scientific publications.
Results
Genetic predisposition, inflammation and abnormal immune response are responsible for the pathogenesis of MM. The initiating genomic event occurs during B cell maturation and clonal plasma cells are disseminated within the bone marrow (BM). This early stage is called monoclonal gammopathy of undetermined significance. The next stage of asymptomatic myeloma, shows a BM infiltration >10%. End organ damage defines symptomatic MM requiring treatment. According to most recent studies MM is characterized by spatial clonal heterogeneity, with aggressive clones frequently being restricted to focal lesions and therefore not being detectable at the iliac crest. Aggressive clones often present with complete inactivation of tumor suppressor genes, such as TP53 and are selected during treatment, which explains the difficulties in treating relapsed MM.
Conclusion
The tumor biology determines the progression of MM and underlies the heterogeneous response to treatment, which can be observed despite intensive treatment.
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L. Rasche und N. Weinhold geben an, dass kein Interessenkonflikt besteht.
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Rasche, L., Weinhold, N. Pathogenese des Multiplen Myeloms. Internist 60, 3–9 (2019). https://doi.org/10.1007/s00108-018-0529-8
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DOI: https://doi.org/10.1007/s00108-018-0529-8
Schlüsselwörter
- Monoklonale Gammopathie unklarer Signifikanz
- Schwelendes Multiples Myelom
- Klonale Evolution
- Erkrankungsprogression
- Tumorheterogenität