METHODS: A 74-year-old man was admitted to the emergency room following the finding of severe macrocytic anaemia during blood tests performed that same day, in particular the patient showed a profound asthenia dating back several months. The anamnesis was silent and the patient was not taking any medications. The blood examination showed an extremely high White Blood Cell count and findings of AIHA in CLL-type mature B-cell lymphoproliferative neoplasia. Genetic investigations: Conventional karyotyping was performed and it obtained a trisomy 8 and an unbalanced translocation between the short arm of chromosome 6 and the long arm of chromosome 11, concurrent with interstitial deletions in chromosomes 6q and 11q that could not be defined in detail. Molecular cytogenetics (FISH) analyses revealed Ataxia Telangiectasia Mutated (ATM) monoallelic deletion (with loss of ATM on derivative chromosome 11) and retained signals for TP53, 13q14 and centromere 12 FISH probes. TP53 and IGHV were not mutated. Array-CGH confirmed trisomy of the entire chromosome 8 and allowed us to resolve in detail the nature of the unbalanced translocation, revealing multiple regions of genomic losses on chromosomes 6 and 11.
CONCLUSIONS: The present case report is an unusual CLL case with complex karyotype and refinement of all breakpoints at the gene level by the genomic array. From a genetic point of view, the case under study presented several peculiarities.
CONCLUSIONS: We report the genetic findings of a CLL patient with abrupt disease onset, so far responding properly to treatments despite the presence of distinct genetic adverse traits including ATM deletion, complex karyotype and chromosome 6q chromoanagenesis event. Our report confirms that interphase FISH alone is not able to provide an overview of the whole genomic landscape in selected CLL cases and that additional techniques are required to reach an appropriate cytogenetic stratification of patients.
方法:一名74岁的男子在当天进行血液检查时发现严重的大细胞性贫血后被送进急诊室,特别是该患者表现出几个月前的严重虚弱。回忆是沉默的,患者没有服用任何药物。血液检查显示,在CLL型成熟B细胞淋巴增殖性肿瘤中,白细胞计数和AIHA的发现极高。遗传研究:进行了常规的核型分析,它获得了8三体和6号染色体短臂与11号染色体长臂之间的不平衡易位,同时染色体6q和11q中的间质缺失无法详细定义。分子细胞遗传学(FISH)分析显示共济失调性毛细血管扩张突变(ATM)单等位基因缺失(在衍生染色体11上丢失了ATM),并保留了TP53,13q14和着丝粒12FISH探针的信号。TP53和IGHV未发生突变。Array-CGH证实了整个8号染色体的三体性,并使我们能够详细解决不平衡易位的性质,揭示了染色体6和11上的多个基因组丢失区域。
结论:本病例报告是一个不寻常的CLL病例,具有复杂的核型和基因组阵列在基因水平上的所有断点的细化。从基因的角度来看,正在研究的案例呈现出几个特点。
结论:我们报告了一名突发性疾病的CLL患者的遗传发现,到目前为止,尽管存在不同的遗传不良特征,包括ATM缺失,复杂核型和染色体6q显色事件。我们的报告证实,单独的间期FISH无法提供选定CLL病例的整个基因组景观的概述,并且需要其他技术来达到患者的适当细胞遗传学分层。