Chromosomal Translocations in CLL

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Chromosomal translocations are associated with poor prognosis in

chronic lymphocytic leukemia

Mayr, R Speicher, M Kofler, Raymund Buhmann,

Strehl, e Busch, Hallek, and Clemens-

Wendtner*

GSF-National Research Center for Environment and Health, Munich,

Germany; Medical Clinic III, Klinikum rosshadern Medical Center,

Ludwig-Maximillians-University of Munich, Munich, Germany; Institute

of Human Genetics, Technical University of Munich, Munich, Germany

GSF-National Research Center for Environment and Health, Munich,

Germany; Institute of Human Genetics, Technical University of Munich,

Munich, Germany

GSF-National Research Center for Environment and Health, Munich,

Germany; Medical Clinic III, Klinikum rosshadern Medical Center,

Ludwig-Maximillians-University of Munich, Munich, Germany; Medical

Clinic I, University of Cologne, Cologne, Germany

GSF-National Research Center for Environment and Health, Munich,

Germany; Medical Clinic III, Klinikum rosshadern Medical Center,

Ludwig-Maximillians-University of Munich, Munich, Germany

Medical Clinic, University of Bonn, Bonn, Germany

Institute of Medical Statistics and Epidemiology, Technical

University of Munich, Munich, Germany

* Corresponding author; email: clemens.wendtner@....

In CLL chromosomes usually evade detailed cytogenetic analyses, as

cells poorly respond to the traditionally used set of mitogens. We

applied novel technologies, i.e. 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 a detailed

chromosome analysis in 96 CLL patients. This approach revealed that

translocations occur in 33 of 96 (34%) of our patients with CLL. The

presence of translocations defines a new prognostic subgroup as these

patients have a highly significant shorter median treatment-free

survival (24 mo vs. 106 mo; p<0.001) and a significantly inferior

overall survival (median OS: 94 mo) compared to patients without

translocations (346 mo; p<0.001). In a multivariate analysis,

including Binet stage, presence of a complex karyotype, CD38

expression and 17p deletions, translocations proved to be the

prognostic marker with the highest impact for an unfavorable clinical

outcome (p<0.001). In summary, we identified a new subgroup of

patients with CLL defined by chromosomal translocations and poor

prognosis. Our data may facilitate the identification of molecular

events crucial for transforming activity in this disease and should

have implications for a risk-adapted clinical management of patients

with CLL.