Molecular analyses of chromosome 12 in chronic lymphocytic leukemia.

Trisomy 12 is the most common chromosomal aberration in chronic B lymphocytic leukemia (B-CLL). In this study we have investigated trisomy 12 and posed two major questions: (a) What is the origin of the third copy of chromosome 12? and (b) What is the proportion of trisomy 12 cells in malignant clones with this aberration? The origin of an extra copy of chromosome 12 in lymphocytes from patients with B-CLL was studied by the use of probes detecting restriction fragment length polymorphisms on this chromosome. In all six patients that were evaluable, the third copy was derived from a simple duplication of one of the original chromosomes. In none of these patients nor in four patients with two copies of chromosome 12 were losses of the homologue observed. When studying metaphase cells from some CLL patients with trisomy 12, a large proportion of the cells are found to have a normal karyotype. In this study the fraction of normal metaphases was not matched by a similar fraction of cells lacking trisomy 12, as judged by scanning densitometry of hybridization bands. Thus, normal metaphases appear to be derived from a small fraction of easily stimulated probably nonmalignant cells and not from a large second population of malignant cells with a normal karyotype.