Skip to ContentSkip to Navigation
About usNews and EventsNews articles

The use of statins in acute myeloid leukemia

28 September 2011

PhD ceremony: Ms. K. van der Weide, 14.45 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: The use of statins in acute myeloid leukemia

Promotor(s): prof. E. Vellenga, prof. E.G.E. de Vries en prof. F. Kuipers

Faculty: Medical Sciences

 

Patients with acute myeloid leukemia (AML) display a dysfunctional cholesterol metabolism in their bone marrow cells, as well as increased cholesterol levels in these AML cells upon in vitro exposure to chemotherapy. This is expected to protect the cells from cytotoxic treatment effects. Intervention with this protective pathway is therefore a potential attractive means to improve therapeutic outcome. Statins inhibit cholesterol synthesis by blocking HMG-CoA reductase, the rate-controlling enzyme of the mevalonate pathway. We showed that combining statins with standard chemotherapy or a farnesyltransferase inhibitor induces more cytotoxicity in AML bone marrow samples than the separate compounds. However, a subset of patient samples appeared to be relatively resistant to statin treatment. To distinguish sensitive from insensitive patients, cell lines with different sensitivities were investigated. It appeared that the differences in response to statins are due to differential effects on the isoprenylation route, rather than the cholesterol synthesis route, of the mevalonate pathway. Summarizing, we demonstrated heterogeneity in the effects of statins in AML cells and patients. Also, we may be able to identify AML patients that will most likely benefit from (combination) treatment with statins.


 

Last modified:15 September 2017 3.40 p.m.

More news

  • 16 April 2019

    A thorough characterization of structural variants in human genomes

    Human genomes vary quite a bit from individual to individual. These differences include single nucleotide changes, or “spelling mistakes” in the DNA sequence, but even more variation comes from structural variants, which include additions, deletions...

  • 02 April 2019

    ‘Sense of loss drives voting behaviour’

    ‘Everybody here loves that academia has returned to Friesland. We teach, carry out research and think along about solutions to problems that are relevant for Friesland,’ says Caspar van den Berg, Professor of Global and Local Governance at the UG Campus...

  • 02 April 2019

    UMCG onderzoekt behandeling tegen geheugenachteruitgang ouderen

    Is het mogelijk om achteruitgang van geheugen en denkvermogen bij ouderen te remmen door hun hersenen letterlijk actiever te maken? Kan stimulatie met zwakke stroompjes op de schedel de veerkracht van hersenen versterken? Hersenonderzoekers van het...