[Chronic lymphoid leukemia: a single disease or 2 distinct diseases?].
Chronic Lymphocytic Leukemia (CLL) most commonly arises from a malignant clone of B cells with a characteristic phenotype, an autoreactive activity and an increased resistance to apoptosis. It is far from uniform in presentation and clinical course. About one-third of patients never require treatment and have a long survival; in another third an initial indolent phase is followed by progression of the disease; the remaining third of patients have aggressive disease at the outset and need immediate treatment. During recent years the development of biologic markers has allowed a better definition of prognosis in CLL. Serum levels of beta 2-microglobulin, LDH, and soluble CD23 can help predict disease activity, but the presence in the leukemic B cells of cytogenetic abnormalities like 11q or 11p deletions, the presence of the CD38 marker or somatic mutations in the immunoglobulin heavy chain genes are better predictors of rapid progression and survival. These recent results could suggest that there are two types of chronic lymphocytic leukemia: one arises from relatively less differentiated (immunologically naive) B cells with unmutated heavy chain genes, and has a poor prognosis; the other evolves from more differentiated B cells (memory B cells) with somatically mutated heavy chain genes, and has a good prognosis. However, all CLL patients share a same morphology, phenotype and overexpression of the bcl-2 and p27Kip1. In addition, recent data derived from gene expression profiling analysis failed to clearly distinguish unmutated and mutated cases and favor the view that all cases of CLL have a common cell origin and/or a common mechanism of malignant transformation.
Dighiero
Guillaume
G
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris. dighiero@pasteur.fr
D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology; D003937:Diagnosis, Differential; D005838:Genotype; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D009154:Mutation; D011379:Prognosis