Chronic lymphocytic leukemia (CLL) is the most common leukemia of adults of Western world. It is a heterogeneous disease with a diverse clinical course. Within CLL occurs also atypical form of CLL. Atypical CLL is characterized by a more aggressive course of the disease and a shorter survival of patients than in typical CLL. Due to the morphological and immunophenotypical heterogeneity of the disease diagnosis is uncertain in small proportion of patients with CLL. A particularly challenging is a differential diagnosis between atypical CLL and mantle cell lymphoma (MCL). Three main prognostic factors in CLL are: cytogenetic aberrations, which are determined by fluorescence in situ hybridization (FISH), the expression of specific proteins (primarily CD38 and ZAP70) and IGHV mutation status of CLL clone. Cytogenetic rearrangements are detected in up to 80% of CLL patients. They are crucial for treatment descision and as prognostic factor, rather than in establishment of diagnosis. These are trisomy of chromosome 12 and deletions of chromosomal regions 13q14, 11q22 (ATM) and 17p13 (TP53). Chromosome 14q32 translocations involving immunoglobulin heavy chain gene (IGH) are rare in CLL, and their determination is not yet prescribed by diagnostic guidelines. Since it is assumed that they have unfavorable prognostic significance, we determine their frequency in Slovenian CLL patients with others aberrations that have a prognostic impact. Separately, we treated a group of patients with typical CLL, atypical CLL and a group of patients with an unfavorable course of the disease without any of significant adverse cytogenetic rearrangements (del(17p13) or del(11q23)). The most common rearrangement in Slovenian patients with CLL is a deletion of chromosomal region 13q14, followed by a deletion of the gene ATM, trisomy 12, deletion of the gene TP53 and as expected, IGH gene translocations is the rarest. In the group of patients with atypical CLL departed incidence of trisomy 12, which was observed in half of the patients. Between typical and atypical CLL the difference in the frequency of trisomy 12 is statistically significant (p=0.0114). CD38 was more often expressed in patients with atypical CLL than in patients with typical CLL, but the difference between groups was not statistically significant (p=0.4440). In 46,9% of patients with atypical CLL immunophenotyp that corresponded to MCL was determined, but with the FISH analysis for MCL characteristic translocation t(11;14) was not confirmed. Because of that, we have reallocated them into a group of patients with atypical CLL. Therefore, it is necessary that the basic panel of DNA probes includes a DNA probe that is specific for the translocation t(11;14), which at the same time also determines other IGH gene rearrangements. We have found IGH rearrangements in 2/85 (2.3%) patients with typically CLL, in 2/24 (8.3%) patients with atypical CLL and in 2/17 (11.8%) patients with aggressive course of the disease, but the difference between these groups was not statistically significant. In two patients with the IGH gene rearrangement translocation t(2;14) was detected, in two translocation t(14;18), in one translocation t(8;14), in one translocation t(14;19), and in one patient a biallelic rearrangement of IGH gene. In two patients we were not able to determine the partner chromosome involved in IGH gene rearrangement.
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