Diagnosis, surveillance, and management of familial leukemia
Diagnosis, surveillance, and management of familial leukemia
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家族性白血病的诊断、监测和治疗
DOI：
10.11406/rinketsu.59.2290
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
盛武 浩
中科院分区：
文献类型：
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作者：
Tomohiro Hirade;Mariko Abe Chie Onishi;Takeshi Taketani;Seiji Yamaguchi;Seiji Fukuda;盛武 浩
最近，综合基因组分析的现代技术已确定源自肿瘤细胞的体细胞突变和种系突变是遗传性家族性白血病的致病基因，其中众所周知的范可尼贫血和李法美尼综合征。致病性种系突变发生在多种途径中，影响DNA修复、核糖体生物发生、端粒生物学、造血转录因子、肿瘤抑制因子、中性粒细胞发育和其他关键细胞过程。种系突变的临床表现呈现出广泛的表型谱，患者表现出先天性异常、早发性骨髓增生异常综合征或在发展为白血病之前没有任何医疗问题。使用基因测试来识别这些受影响的人将大大有利于癌症监测和随后的治疗干预。尽管家族性白血病治疗通常集中于儿童，但临床医生必须认识到家族性白血病可以发生在任何年龄，甚至老年人中。诊断后的遗传咨询至关重要，建议立即转诊给每种疾病的专家。
Recently, the modern technique of comprehensive genomic analysis has identified both somatic mutations originating from tumor cells and germline mutations as causative genes of inherited familial leukemias among which Fanconi anemia and Li-Fraumeni syndrome are well known. Pathogenic germline mutations occur in various pathways, affecting DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, neutrophil development, and other critical cellular processes. The clinical manifestations of germline mutations present a wide phenotypic spectrum of patients displaying congenital anomalies, early-onset myelodysplastic syndrome, or no medical problems until the developing leukemia. The use of genetic tests to identify these affected persons will significantly benefit cancer surveillance and subsequent therapeutic interventions. Although familial leukemia treatment usually focuses on children, it is important for clinicians to recognize that familial leukemias can occur at any age, even among older adults. Genetic counseling after diagnosis is essential, and an immediate referral to experts in each disease is recommended.