Evolution of Karyotypes in Acute Nonlymphocytic Leukemia’

Serial samples of leukemic cells were obtained from 60 of 90 patients with acute nonlymphocytic leukemia for chromosome analysis with banding techniques, so that we could determine whether a nonrandom pattern of karyotypic evolution is associated with acute nonlymphocytic leukemia. Evolution of the karyotype was observed in 17 of these patients, 7 of whose chromosomes were initially normal and 10 of whose chromosomes were initially abnormal. All 10 abnormal patients had chromosomes with structural rearrangements in the initial sample; 8 of the 10 also showed loss of one or more chromosomes initially. The most frequent evolutionary change was a gain of one or more chromosomes (in 12 of the 17 patients). Ten of the 12 patients who acquired one or more additional chromosomes had an extra chromosome 8, and 6 had an extra chromosome 18. Other evolutionary changes included structural rearrangements (8 patients), loss of a chromosome (4 patients), and loss of a marker (2 patients). These various changes sometimes occurred in combination. The incidence of karyotypic evolution and the type and frequency of particular evolutionary changes were similar in patients who were initially normal and in those who were initially abnormal. In all but one of the initially abnormal patients, karyotypic evolution involved the original cytogenetically abnormal clone. In no instance was a clone of chromosomally abnormal cells detected when the bone marrow was morphologically normal; single abnormal cells of clonal origin, however, were observed on a few occasions when bone marrow morphology was normal. Acute non-lymphocytic leukemia patients whose karyotype evolved tended to have relatively long survival times. However, the median survival after the actual onset of evolution was relatively short (2 months), and the response to further therapy was poor. Karyotypic changes can have prognostic significance which may be useful in decisions on the aggressiveness of further therapy.