Refractory T-cell/histiocyte-rich large B-cell lymphoma in a patient with ataxia-telangiectasia caused by novel compound heterozygous variants in ATM
Refractory T-cell/histiocyte-rich large B-cell lymphoma in a patient with ataxia-telangiectasia caused by novel compound heterozygous variants in ATM
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DOI：
10.1007/s12185-021-03203-w
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发表时间：
2021-08-23
影响因子：
2.1
通讯作者：
Kure, Shigeo
中科院分区：
文献类型：
--
作者：
Sato, Daichi;Moriya, Kunihiko;Kure, Shigeo
共济失调-毛细血管扩张症（Ataxia-telangiectasia，A-T）是一种常染色体隐性遗传的染色体断裂综合征，由ATM基因突变引起，ATM基因编码的蛋白激酶在细胞对DNA损伤的反应中起主要作用。大约10%的A-T患者发生淋巴恶性肿瘤。对恶性肿瘤化疗的极端敏感性导致的死亡已有报道，A-T中的癌症治疗非常困难，需要仔细监测和个性化方案。我们报告的情况下，一个12岁的女孩与A-T诊断在3岁与伊加缺乏症和反复肺部感染。桑格测序显示ATM基因的复合杂合性，其中携带两个新的突变。12岁时，她患上了IV期富含T细胞/组织细胞的大B细胞淋巴瘤。肿瘤对化疗有抵抗力，她不幸死于疾病快速进展引发的心功能不全和多器官功能衰竭。对于患有A-T和晚期B非霍奇金淋巴瘤的儿童的治疗方法必须加以改进。
Ataxia-telangiectasia (A-T) is an autosomal recessive chromosomal breakage syndrome caused by mutation of the ATM (A-T mutated) gene, which encodes a protein kinase that has a major role in the cellular response to DNA damage. Approximately, 10% of A-T patients develop lymphoid malignancies. Deaths caused by extreme sensitivity to chemotherapy for malignancy have been reported, and cancer treatment in A-T is extraordinarily difficult, needing careful monitoring and individualized protocols. We report the case of a 12-year-old girl with A-T diagnosed at the age of 3 in association with IgA deficiency and recurrent pulmonary infections. Sanger sequencing revealed compound heterozygosity of the ATM gene, which bore two novel mutations. At the age of 12, she developed stage IV T-cell/histiocyte-rich large B-cell lymphoma. The tumor was resistant to chemotherapy, and she unfortunately died of cardiac insufficiency and multiple organ failure induced by rapid progression of the disease. The treatment approach for children with A-T and advanced-stage B-non-Hodgkin lymphoma must be refined.