Přehled o publikaci

In a subset of patients with chronic lymphocytic leukemia (CLL), multiple B-lymphocyte clones with distinct B-cell receptors transform simultaneously. Each clone may carry different genomic aberrations, posing a risk for unfavorable clonal evolution. In our previous study, we observed that the proportion of clones can change over the course of the disease, with a previously minor population potentially becoming dominant. Through diagnostic assessment of the mutational status of clonal immunoglobulin heavy chain (IGH) rearrangements, we identified 234 cases of multi-clonal CLL in a cohort of 3,051 CLL patients. These included 209 biclonal, 23 triclonal, and 2 tetraclonal cases. In 160 cases, the coexisting clones had concordant IGH mutational status (105 mutated, 55 unmutated), while 74 cases exhibited discordant IGH mutational profiles. In 97 patients, repeated assessments were performed over time (median interval between the first and last examination: 3.6 years). In 51 patients, one or more clones disappeared in later samples, while 21 patients developed a new clone. In four cases, the dominant clone was replaced by another. To gain deeper insights into the genomic composition of multi-clonal CLL, we analyzed tumor DNA from a representative group of multi-clonal cases using the LYNX NGS panel, designed to detect markers of the most common lymphoid neoplasms. This panel allows the identification of immunoglobulin rearrangements, chromosomal aberrations, and mutations in selected genes. We compared clonal proportions across different clones in parallel with amplicon-based IGH NGS sequencing. The results provided a comprehensive characterization of the tested multi-clonal CLL cases and their clonal evolution.