Proteasome inhibitors are the backbone in the treatment of multiple myeloma with 3 of its representatives (bortezomib, carfilzomib, and ixazomib) having already been approved. There is a different situation altogether in the treatment of amyloid light chain (AL) amyloidosis where owing to the rarity of this entity neither of these drugs has currently gained approval. Amyloid light chain plasma cells are possibly more vulnerable to bortezomib than myeloma plasmocytes because of a slightly distinct mechanism of action, which is described in depth in this manuscript. Bortezomib is highly active and rapidly effective as a single agent and even more potent in combination with dexamethasone and alkylators. Bortezomib-based regimens have become a standard part of the initial treatment of AL amyloidosis in the majority of centers. We have reviewed all available data on bortezomib in various combinations and settings. Carfilzomib seems to be effective but also toxic in these fragile patients with a high rate of cardiac events. Oral ixazomib has shown a surprisingly high efficacy with manageable toxicity and has received the Food and Drug Administration Breakthrough Therapy designation in 2014 for relapsed AL amyloidosis patients. In this review we have comprehensively described the current available knowledge of these 3 proteasome inhibitors and their use in AL amyloidosis.
- Klíčová slova
- Amyloidosis, NEOD001, bortezomib, carfilzomib, ixazomib, multiple myeloma,
- MeSH
- inhibitory proteasomu aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- mnohočetný myelom farmakoterapie patologie MeSH
- primární amyloidóza farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- inhibitory proteasomu MeSH
AIMS: Some types of monoclonal gammopathies are typified by a very limited availability of aberrant cells. Modern research use high throughput technologies and an integrated approach for detailed characterisation of abnormal cells. This strategy requires relatively high amounts of starting material which cannot be obtained from every diagnosis without causing inconvenience to the patient. The aim of this methodological paper is to reflect our long experience with laboratory work and describe the best protocols for sample collection, sorting and further preprocessing in terms of the available number of cells and intended downstream application in monoclonal gammopathies research. Potential pitfalls are also discussed. METHODS: Comparison and optimisation of freezing and sorting protocols for plasma cells in monoclonal gammopathies, followed by testing of various nucleic acid isolation and amplification techniques to establish a guideline for sample processing in haemato-oncology research. RESULTS: We show the average numbers of aberrant cells that can be obtained from various monoclonal gammopathies (monoclonal gammopathy of undetermined significance/light chain amyloidosis/multiple myeloma (MM)/MM circulating plasma cells/ minimal residual disease MM-10 123/22 846/305 501/68 641/4000 aberrant plasma cells of 48/30/10/16/37×106 bone marrow mononuclear cells) and the expected yield of nucleic acids provided from multiple isolation kits (DNA/RNA yield from 1 to 200×103 cells was 2.14-427/0.12-123 ng). CONCLUSIONS: Tested kits for parallel isolation deliver outputs comparable with kits specialised for just one type of molecule. We also present our positive experience with the whole genome amplification method, which can serve as a very powerful tool to gain complex information from a very small cell population.
- Klíčová slova
- DNA, HAEMATO-ONCOLOGY, METHODOLOGY, MYELOMA,
- MeSH
- DNA izolace a purifikace MeSH
- konzervace krve metody MeSH
- krevní bankovnictví metody MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- odběr vzorku krve metody MeSH
- paraproteinemie krev MeSH
- reagenční diagnostické soupravy MeSH
- RNA izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA MeSH
- reagenční diagnostické soupravy MeSH
- RNA MeSH
