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Melphalan flufenami...
Melphalan flufenamide inhibits osteoclastogenesis by suppressing proliferation of monocytes
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- Byrgazov, Konstantin (author)
- Oncopeptides AB, Stockholm, Sweden.
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- Lind, Thomas, Docent, 1965- (author)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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- Rasmusson, Annica J. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Klinisk farmakogenomik och osteoporos,Cervenka: Psykiatri
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- Andersson, Claes (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Slipicevic, Ana (author)
- Oncopeptides AB, Stockholm, Sweden.
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- Lehmann, Fredrik (author)
- Oncopeptides AB, Stockholm, Sweden.
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- Gullbo, Joachim (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin,Experimentell och klinisk onkologi
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- Melhus, Håkan (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Larsson, Rolf (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin,Klinisk immunologi
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- Fryknäs, Mårten (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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Oncopeptides AB, Stockholm, Sweden Klinisk farmakogenomik och osteoporos (creator_code:org_t)
- Elsevier, 2021
- 2021
- English.
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In: Bone Reports. - : Elsevier. - 2352-1872. ; 15
- Related links:
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https://doi.org/10.1...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Myeloma bone disease is a major complication in multiple myeloma affecting quality of life and survival. It is characterized by increased activity of osteoclasts, bone resorbing cells. Myeloma microenvironment promotes excessive osteoclastogenesis, a process of production of osteoclasts from their precursors, monocytes. The effects of two anti-myeloma drugs, melphalan flufenamide (melflufen) and melphalan, on the activity and proliferation of osteoclasts and their progenitors, monocytes, were assessed in this study. In line with previous research, differentiation of monocytes was associated with increased expression of genes encoding DNA damage repair proteins. Hence monocytes were more sensitive to DNA damage-causing alkylating agents than their differentiated progeny, osteoclasts. In addition, differentiated progeny of monocytes showed increased gene expression of immune checkpoint ligands which may potentially create an immunosuppressive microenvironment. Melflufen was ten-fold more active than melphalan in inhibiting proliferation of osteoclast progenitors. Furthermore, melflufen was also superior to melphalan in inhibition of osteoclastogenesis and bone resorption. These results demonstrate that melflufen may exert beneficial effects in patients with multiple myeloma such as reducing bone resorption and immunosuppressive milieu by inhibiting osteoclastogenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Osteoclastogenesis
- Bone resorption
- Melflufen
- Melphalan
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Byrgazov, Konsta ...
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Lind, Thomas, Do ...
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Rasmusson, Annic ...
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Andersson, Claes
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Slipicevic, Ana
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Lehmann, Fredrik
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show more...
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Gullbo, Joachim
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Melhus, Håkan
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Larsson, Rolf
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Fryknäs, Mårten
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Bone Reports
- By the university
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Uppsala University