Chromosomal abnormalities in bone marrow cells in relapse of chronic lymphocytic leukemia

Abstract

The genetic mechanism of resistance to chemotherapy in chronic lymphocytic leukemia (CLL) is yet to be established. We aimed to determine molecular cytogenetic irregularities in chromosomes of bone marrow cells (BM) in relapse of CLL. For this, a study was carried out with 63 patients including 25 women and 38 men, aged from 36 to 73 years (average age was 57 years). Cytogenetic data showed that karyotypes, according to the clone structure, were represented into 10 groups: normal; normal/near tetraploid; abnormal/normal; abnormal/near tetraploid/normal; clonal evolution; clonal evolution/normal; clonal evolution/near tetraploid/normal; independent clones; independent/normal; independent/near tetraploid/normal clones. Various structural rearrangements were detected in chromosomes such as translocations, deletions, insertions and duplications. However, deletions in chromosomes were found to be dominant in 63.8% cases involving the band positions of especially 17p12, 13q12–q14, 11q14 and 11q23. The complexity was shown by the presence of one to four abnormalities in one karyotype using i-FISH methodology. Conventional cytogenetic and molecular cytogenetic analyses may indicate that chromosome rearrangements are multilevel process in formation of resistant karyotypes either through the loss of (1) tumour suppressor genes in the areas with bands 13q14, 13q34 and 17p13.1 (2) and/or the loss of regulation of ATM gene expression in the band position 11q22.3. The results obtained using both methods have demonstrated the presence of a heterogeneous cell population with a diverse degree of resistance to chemotherapy in CLL.