title: Screening for cytotoxic compounds in poor-prognostic chronic lymphocytic leukemia.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: Maria
authors: M
authors: Norberg
authors: Elin
authors: E
authors: Lindhagen
authors: Meena
authors: M
authors: Kanduri
authors: Linda
authors: L
authors: Rickardson
authors: Christer
authors: C
authors: Sundström
authors: Kostas
authors: K
authors: Stamatopoulos
authors: Richard
authors: R
authors: Rosenquist
authors: Anna
authors: A
authors: Åleskog
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002877:Chromosomes, Human; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents