Bilous N, Abramenko I, Chumak A, Dyagil I, Martina Z
Department of Clinical Immunology, National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv 02000, Ukraine.
Department of Hematology, National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv 02000, Ukraine.
Exp Oncol. 2020 Mar;42(1):60-65. doi: 10.32471/exp-oncology.2312-8852.vol-42-no-1.14214.
Some clinical and biological features indicating an unfavorable course of the disease were found in ionizing radiation (IR) - related chronic lymphocytic leukemia (CLL) patients. The MYC proto-oncogene is considered to contribute to CLL pathogenesis. Increased MYC copy number is associated with poor prognosis in CLL.
To investigate the frequency of MYC gene copy number amplification in IR-exposed CLL patients and relate the findings to the MYC mRNA 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 70 IR-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 TP53 and SF3B1 mutations, while one case was identified, where MYC amplification and NOTCH1 mutation coincided simultaneously. Regarding clinical outcome, the MYC aberrations were associated with a shorter time to first treatment (3 vs 25 months, p = 0.008) as well as reduced overall survival (60 vs 139 months).
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 TP53 and SF3B1 mutations.
在与电离辐射（IR）相关的慢性淋巴细胞白血病（CLL）患者中发现了一些表明疾病进程不利的临床和生物学特征。MYC原癌基因被认为与CLL发病机制有关。MYC拷贝数增加与CLL预后不良相关。
研究IR暴露的CLL患者中MYC基因拷贝数扩增的频率，并将研究结果与MYC mRNA水平、不良预后突变（TP53、SF3B1、NOTCH1）的存在情况以及患者的预后相关联。
采用实时定量聚合酶链反应（PCR）对70例IR暴露的CLL患者进行MYC拷贝数分析。通过实时定量逆转录PCR测量MYC mRNA表达。
5.7%的病例中存在MYC基因拷贝数增加。MYC拷贝数增加与MYC mRNA增加之间存在统计学显著关联（p < 0.014）。此外，在一名患者中发现了MYC基因座的体细胞缺失。大多数检测到MYC异常的患者（80%）此前未接受过治疗，这表明这些病变可能在疾病进程早期出现。发现MYC异常与高危TP53和SF3B1突变相互排斥，而有一例同时出现了MYC扩增和NOTCH1突变。关于临床结局，MYC异常与首次治疗时间缩短（3个月对25个月，p = 0.008）以及总生存期缩短（60个月对139个月）相关。
我们的数据表明，MYC异常可能是IR相关CLL中的早期事件，并且在不存在高危TP53和SF3B1突变的情况下促成侵袭性疾病的发展。
