Sökning: id:"swepub:oai:lup.lub.lu.se:990875d6-a5e3-497e-a1aa-53d653f59f62" >
Inhibition of UDP-g...
Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy
-
Pavlova, Elena V. (författare)
-
Archer, Joy (författare)
-
Wang, Susan Z. (författare)
-
visa fler...
-
Dekker, Nick (författare)
-
Aerts, Johannes M. F. G. (författare)
-
- Karlsson, Stefan (författare)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
-
Cox, Timothy M. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2014-12-10
- 2015
- Engelska.
-
Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 235:1, s. 113-124
- Relaterad länk:
-
http://dx.doi.org/10...
-
visa fler...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Clonal B-cell proliferation is a frequent manifestation of Gaucher disease-a sphingolipidosis associated with a high risk of multiple myeloma and non-Hodgkin lymphoma. Gaucher disease is caused by genetic deficiency of acid -glucosidase, the natural substrates of which (-d-glucosylceramide and -d-glucosylsphingosine) accumulate, principally in macrophages. Mice with inducible deficiency of -glucosidase [Gba(tm1Karl/tm1Karl)Tg(MX1-cre)1Cgn/0] serve as an authentic model of human Gaucher disease; we have recently reported clonal B-cell proliferation accompanied by monoclonal serum paraproteins and cognate tumours in these animals. To explore the relationship between B-cell malignancy and the biochemical defect, we treated Gaucher mice with eliglustat tartrate (GENZ 112638), a potent and selective inhibitor of the first committed step in glycosphingolipid biosynthesis. Twenty-two Gaucher mice received 300mg/kg of GENZ 112638 daily for 3-10 months from 6 weeks of age. Plasma concentrations of -d-glucosylceramide and the unacylated glycosphingolipid, -d-glucosylsphingosine, declined. After administration of GENZ 112638 to Gaucher mice for 3-10 months, serum paraproteins were not detected and there was a striking reduction in the malignant lymphoproliferation: neither lymphomas nor plasmacytomas were found in animals that had received the investigational agent. In contrast, 14 out of 60 Gaucher mice without GENZ 112638 treatment developed these tumours; monoclonal paraproteins were detected in plasma from 18 of the 44 age-matched mice with Gaucher disease that had not received GENZ 112638. Long-term inhibition of glycosphingolipid biosynthesis suppresses the development of spontaneous B-cell lymphoma and myeloma in Gaucher mice. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- Gaucher disease
- glycosphingolipids
- lymphoma
- myeloma
- UDP-glucosylceramide synthase
- GBA1 deficiency
- eliglustat
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas