Abstract

To investigate the frequency ofMYCgene copy number amplification in IR-exposed CLL patients and relate the findings to theMYCmRNA levels, the presence of unfavourable prognosis mutations (TP53, SF3B1, NOTCH1), and patient`s outcome. The analysis of MYC copy number was carried out by real-time quantitative polymerase chain reaction (PCR) in 70IR-exposed CLL patients. The MYC mRNA expression was measured by real-time quantitative reverse transcription PCR. Increased MYC gene copy number was present in 5.7% of cases. There was a statistically significant association between increased MYC copy number and increased MYC mRNA (p<0.014). Additionally, somatic deletion in MYC locus was found in one patient. Most of patients (80%) with detected MYC aberrations were previously untreated, suggesting that these lesions might occur early in the course of the disease. The MYC aberrations were found mutually exclusive with high risk TP53and SF3B1mutations, while one case was identified, where MYC amplification and NOTCH1mutation coincided simultaneously. Regarding clinical outcome, the MYC aberrations were associated with a shorter time to first treatment (3vs 25months, p = 0.008) as well as reduced overall survival (60vs 139months). Our data suggest that MYC aberrations might be an early event in IR-related CLL and contribute to aggressive disease development in the absence of high risk TP53and SF3B1mutations.

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