CHROMOSOME-ABERRATIONS IN ATYPICAL CHRONIC LYMPHOCYTIC-LEUKEMIA - A CYTOGENETIC AND INTERPHASE CYTOGENETIC STUDY

To define better the chromosomal profile of atypical chronic lymphocyt ic leukemia (aCLL), cytogenetic and interphase cytogenetic studies wer e performed in 43 cases, using mitogen-stimulated cultures and DNA pro bes detecting the two most frequently occurring aberrations in CLL, ie +12 and 13q14 deletions. All cases showed monoclonal CD5/CD19-positiv e lymphocytosis, with more than 10% large lymphocytes and/or prolympho cytes in peripheral blood smears and reactivity with FMC7, or bright e xpression of surface immunoglobulins in a fraction of the cases. Karyo type aberrations were detected in 27 of 43 cases (62.8%). Recurrent ch romosome changes were +12(nine cases), 13q14 aberrations (five cases), 11q anomalies (three cases), 6q21-q23 abnormalities and 4q anomalies with different breakpoints (two cases each). Additional chromosome cha nges were seen in four cases with +12, in three cases with 13q14 anoma lies, in two cases with 11q anomalies, in one case with 6q and 4q anom alies, Trisomy 12 was associated with 13q14 anomalies in three cases, one of which also had an 11q abnormality; other associations, found in one case each, were: 13q14 deletion with a 6q anomaly, 11q anomaly wi th 13q- and 7q-, a 6q anomaly with 7q- and +12. Interphase cytogenetic s confirmed the results of chromosome banding analysis and showed that six patients with normal karyotype or no mitosis in fact had concomit ant +12 and 13q14 deletion in four cases and isolated +12 or 13q14 del etion in one case each, with a resultant 76% overall incidence of cyto genetic abnormalities. The presence of +12, 13q14 deletions, 11q, and 6q21-q23 anomalies in 19 cases was associated with a 2-month median in terval between diagnosis and start of treatment, as compared with a 24 -month median interval in 14 cases with normal karyotype or non-recurr ent chromosome changes (P = 0.003). We conclude that aCLL is character ized by a relatively high incidence of chromosome anomalies, with recu rrent chromosome changes, involving chromosomes 12, 13q14, 6q21q23, 11 q, and, possibly, 4q, The presence of complex karyotypes, with concomi tant abnormalities of 13q, +12, 6q, 11q, suggests that the development of sequential chromosome changes, rather than any single specific ano maly, may underlie leukemogenesis in this cytologic subset of CLL, par tially accounting for the relatively aggressive clinical course.