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Screening for Cytotoxic Compounds in Poor-prognostic Chronic Lymphocytic Leukemia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology. (Rosenquist Brandell)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
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2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 8, 3125-3136 p.Article in journal (Refereed) Published
Abstract [en]

Background/Aim: For chronic lymphocytic leukemia (CLL) patients with poor-prognostic genomic aberrations the therapeutic options are limited. We used the Spectrum Collection library to identify compounds with anti-leukemia activity in high-risk CLL.

Materials and Methods: We identified substances with equal high cytotoxic activity in vitro in samples from poor-prognostic CLL (11q-/17p-, n=3) as compared to those from favourable-prognostic CLL (13q-, n=3). Cell survival was measured by fluorometric microculture cytotoxicity assay.

Results: Out of 2,000 compounds, 65 had a similar effect in both prognostic groups. Fifteen compounds were selected for dose-response experiments in 16 additional CLL samples. Of these compounds, 12 continued to have similar cytotoxicity between prognostic subgroups. Additional experiments demonstrated that in CLL cells with 11q or 17p deletion, 5-azacytidine induced apoptosis in a dose-dependent manner and lipoprotein lipase expression was reduced following orlistat treatment.

Conclusion: Using primary cultures of cells from high-risk CLL patients for compound screening is a feasible approach and that 5-azacytidine and orlistat exemplify substances that exhibit cytotoxicity in poor-risk CLL.

Place, publisher, year, edition, pages
2012. Vol. 32, no 8, 3125-3136 p.
Keyword [en]
Chronic lymphocytic leukemia, poor-risk genomic aberrations, compound library screening, cytotoxicity, 5-azacytidine, orlistat
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-181866ISI: 000306892700015PubMedID: 22843883OAI: oai:DiVA.org:uu-181866DiVA: diva2:558001
Available from: 2012-10-01 Created: 2012-10-01 Last updated: 2017-12-07Bibliographically approved

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PubMedhttp://ar.iiarjournals.org/content/32/8/3125.abstract

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Lindhagen, ElinKanduri, MeenaRickardson, LindaSundström, ChristerRosenquist, RichardAleskog, Anna

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