Complex chromosomal rearrangements in patients with chronic myeloid leukemia

During progression of chronic myeloid leukemia (CML) from the chronic to the accelerated phase and/or blast crisis, clonal evolution with nonrandom secondary aberrations such as +8, +Ph, i(17q), +19, −Y, +21, +17, and −7 is frequently observed. Complex chromosomal rearrangements (CCR) are rather rare, and the significance and frequency of different anomalies are poorly understood. The aim of this study was to determine the chromosomes and chromosomal regions which are involved in CCR during progression of the disease and the frequency of nonrandom changes. Conventional cytogenetics, FISH, and multicolor FISH (mFISH) were used to study karyotypes of 18 CML patients with CCR ascertained by G-banding. Most often involved in CCR were chromosomes 2 (×6); 3, 7, and 17 (×5); 1 and 4 (×4); and 5, 6, 11, and 12 (×3); regions 1q, 2q, 5q, 7p, and 17p; and breakpoints 17p11.2 (×3) and 7p15 (×2). There were no recurrent complex translocations. The present findings demonstrate the very high instability of the genome of malignant cells at the chromosomal level. Precise determination of breakpoints involved in CCR can give new dimension to the understanding of genetic mechanisms which play role in progression of malignant disease.