Determination of MDM2 oncogene activation i̇n chronic lymphocytic leukemia cases

The aim of this study was to evaluate MDM2 gene copy number alterations in Chronic Lymphocytic Leukaemia (CLL) patients with Fluorescent In Situ Hybridization (FISH) technique by using Murine double minute 2 (MDM2) gene-specific probe sets, and also to evaluate the possible relationship between this amplification and the disease course, indication for treatment and drug resistance. Copy number alterations of MDM2 gene which located on chromosome 12 were investigated by FISH technique using metaphase chromosomes obtained from bone marrow aspiration samples for routine chromosome analysis in 40 CLL and 20 Chronic Myeloid Leukemia (CML) patients those followed-up at Akdeniz University Department of Haematology. Additionally, routine FISH and conventional cytogenetics results of the patients were evaluated. MDM2 gene amplification was not observed in patient cohort (CLL) and in control patients (CML). Trisomy 12 FISH signal pattern was observed in 12 out of 40 CLL patients (30%). Furthermore, chromosomal alterations detected by routine FISH analysis in 40 CLL patients were as follows; 17p13 deletion in 16 cases (40%), 13q14 deletion in 13 patients (32.5%), 11q22.3 deletion in 6 patients (15%), and 6q23 deletion in 1 case (2.5%). We thought that, evaluation of MDM2 mRNA expression levels in CLL patients might be conducted due to absence of MDM2 gene copy number alterations. Additionally, evaluation of SNP309 G/G single nucleotide polymorphism in advanced stage CLL patients without MDM2 gene amplification might provide important clues for progression disease. 27 out of the 40 CLL patients (67.5%) were classified as having early stage disease. We can suggest that in the case of progression to advanced stage CLL during the follow-up period, re-evaluation of MDM2 gene copy number alterations will be more useful to explain the relationship between copy number alterations of MDM2 gene and CLL.