Hartmut Döhner

Genetics of B-Cell Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (B-CLL) is the most frequent type of leukemia among adults in the Western world, with an incidence of about 5 cases per 100,000 residents annually (1,2). The disease affects mainly people of advanced age, but about 20% of patients are younger than 55 (3).B-CLL is characterized by the accumulation of lymphocytes that appear morphologically mature but are functionally incompetent in bone marrow, blood, lymph nodes, and other organs, primarily of the lymphatic system (Fig. 1). During the course of the disease, there is increasing suppression of normal hematopoiesis and impairment of organ functions, resulting in B-symptoms, susceptibility to infection, and hemorrhage (Fig. 1). Currently available conventional therapeutic procedures are aimed at palliation. In younger patients, potentially curative approaches like autologous or allogeneic stem cell transplantation and antibody therapies are currently being investigated. The prognosis is influenced by the degree of dissemination of the disease at the time of diagnosis. This is reflected in the prognostic importance of the clinical staging systems defined by Rai and Binet (4,5).Both systems differentiate among early (Rai 0, Binet A), intermediate (Rai I, II; Binet B) and advanced (Rai III, IV; Binet C) stages, which are characterized by different survival times (Fig. 2) (6).However, the prognostic value of clinical staging is limited, especially in early stages, and there is marked heterogeneity in the speed of disease progression within the individual stages. For this reason, there has been intensive work in recent years on the identification of other clinical and biological factors with potential prognostic relevance. Genetic characteristics of the B-CLL cells have attained considerable importance among these factors (7–10).

Chronisch lymphatische Leukämie vom B-Zell-Typ (B-CLL)

Die chronisch lymphatische Leukamie vom B-Zell-Typ (B-CLL) ist mit einer Inzidenz von etwa 5 Fallen pro 100000 Einwohner im Jahr die haufigste Leukamieform des Erwachsenenalters in der westlichen Welt (Rozman u. Montserrat 1995, Zwiebel u. Cheson 1998). Die Erkrankung betrifft vorwiegend Personen im hoheren Lebensalter, wobei etwa 20% der Patienten junger als 55 Jahre sind (Mauro et al. 1999). Die CLL ist durch die Akkumulation morphologisch reif erscheinender, jedoch funktionell inkompetenter Lymphozyten in Knochenmark, Blut, Lymphknoten und anderen Organen vorwiegend des lymphatischen Systems charakterisiert (Abb. 4.1.1b). Im Verlauf der Krankheit kommt es zu einer zunehmenden Verdrangung der Hamatopoese und einer Beeintrachtigung der Organfunktionen mit der Folge von Allgemeinsymptomen, Lymphadenopathien (Abb. 4.1.1a), Infekt- und Blutungsneigung. Derzeit verfugbare konventionelle Therapieverfahren sind von palliativem Charakter.