title: Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia.
abstract: In chronic lymphocytic leukemia (CLL), chromosomes usually evade detailed cytogenetic analyses because cells poorly respond to the traditionally used set of mitogens. We applied novel technologies, such as stimulation of CLL cells either with CD40 ligand or with a combination of CpG-oligodeoxynucleotides and IL-2, to increase the frequency of metaphase spreads for detailed chromosome analysis in 96 patients with CLL. This approach revealed that translocations occurred in 33 of 96 (34%) of our patients with CLL. The presence of translocations defined a new prognostic subgroup because these patients have significantly shorter median treatment-free survival (24 months vs 106 months; P < .001) and significantly inferior overall survival (OS; median, 94 months) than patients without translocations (346 months; P < .001). In multivariate analysis-including Binet stage, complex karyotype, CD38 expression, and 17p deletions-translocation proved to be the prognostic marker with the highest impact for an unfavorable clinical outcome (P < .001). In summary, we identified a new subgroup of patients with CLL defined by chromosomal trans-locations and poor prognosis. Our data may facilitate the identification of molecular events crucial for transforming activity in this disease and should have implications for risk-adapted clinical management of patients with CLL.
authors.affiliation: Gesellschaft für Strahlenforschung (GSF)-National Research Center for Environment and Health, Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Mayr
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
authors.forename: David M
authors.initials: DM
authors.lastname: Kofler
authors.forename: Raymund
authors.initials: R
authors.lastname: Buhmann
authors.forename: John
authors.initials: J
authors.lastname: Strehl
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Clemens-Martin
authors.initials: CM
authors.lastname: Wendtner
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D023201:CD40 Ligand / Q000494:pharmacology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007376:Interleukin-2 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008677:Metaphase; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011379:Prognosis; D015996:Survival Rate; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D023201:CD40 Ligand; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1