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Abstract：
BACKGROUND: Chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries, is a mature B-cell chronic lymphoproliferative disorder characterized by the accumulation of neoplastic CD5+ B lymphocytes, functionally incompetent and usually monoclonal in origin, in bone marrow, lymph nodes and blood. Diagnosis occurs predominantly in elderly patients, with a median age reported between 67 and 72 years. CLL has a heterogeneous clinical course, which can vary from indolent to, less frequently, aggressive forms. Early-stage asymptomatic CLL patients do not require immediate therapeutic intervention, but only observation; treatment is necessary for patients with advanced disease or when \"active disease\" is observed. The most frequent autoimmune cytopenia (AIC) is autoimmune haemolytic anaemia (AHIA). The main mechanisms underlying the appearance of AIC in CLL are not fully elucidated, the predisposition of patients with CLL to suffering autoimmune complications is variable and autoimmune cytopenia can precede, be concurrent, or follow the diagnosis of CLL.
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.
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.
摘要：
背景：慢性淋巴细胞白血病（CLL），西方国家最常见的白血病，是一种成熟的B细胞慢性淋巴增殖性疾病，其特征是肿瘤CD5+B淋巴细胞的积累，功能上无能，通常是单克隆起源，在骨髓中，淋巴结和血液。诊断主要发生在老年患者，据报道，中位年龄在67至72岁之间。CLL具有异质性的临床病程，它可以从惰性到，不那么频繁,侵略性的形式。早期无症状CLL患者不需要立即治疗干预，但只能观察；对于晚期疾病或观察到“活动性疾病”的患者，治疗是必要的。最常见的自身免疫性血细胞减少症（AIC）是自身免疫性溶血性贫血（AHIA）。CLL中AIC出现的主要机制尚未完全阐明，CLL患者自身免疫性并发症的易感性是可变的，自身免疫性血细胞减少症可以发生，并发，或遵循CLL的诊断。
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。
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。
