Cytogenetics in chronic lymphocytic leukemia.

Clonal chromosomal abnormalities in leukemic cells are detected in almost half of studied patients with chronic lymphocytic leukemia (CLL) using cytogenetic analysis of metaphase cells after B-cell mitogen stimulation in vitro, or molecular techniques with fluorescence in situ hybridization on metaphase or interphase cells. One third of the patients with clonal aberrations have trisomy 12, with or without additional changes. A median of about half of the interphase as well as the metaphase cells in cases with trisomy 12 are found to carry the abnormality. A few small studies have found cells with trisomy 12 in a minor percentage of the leukemic cells only. The biological significance of this is unclear. The common interpretation indicating that trisomy 12 is a secondary abnormality is not valid, at least not during clinical disease, because trisomy 12 is never found to appear during the course of the disease. The most frequent structural abnormalities involve the long arm of chromosome 13, mostly in the form of interstitial deletions involving 13q14.3. A 160-kb region between the Rb gene and D13S25, in the vicinity of MGG15 (containing the markers D13S272 and D13S319), and p6E4.5, seems to be the most commonly deleted region, involved in about 40% of 273 tested samples, including 10% of homozygous deletions. It seems likely that this region contains a tumor suppressor gene relevant for the pathogenesis in CLL. Trisomy 12 in CLL is associated with atypical morphology, progressive disease and poor survival, whereas cytogenetic 13q-abnormalities seem to indicate a good prognosis. Complex karyotypes and high proportion of cytogenetically abnormal cells indicate poor survival. No clinical impact of chromosome abnormalities identified by molecular techniques have so far emerged.