Abstract:
Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, some of these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, which have been related to treatment. Several studies have shown that after treatment, HL patients and survivors present persistent chromosomal instability, including nonclonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting nonclonal chromosomal aberrations and genomic chaos in a fraction of noncancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer.
摘要:
霍奇金淋巴瘤(HL)患者的抗癌方案包括高度遗传毒性的药物,这些药物在杀死肿瘤细胞方面非常成功,并在五年内提供90%的无病生存率。然而,这些治疗中的一些没有特定的细胞靶标,破坏癌细胞和正常细胞。因此,HL幸存者有发展新的原发性癌症的高风险,血液和实体瘤,与治疗有关。一些研究表明,治疗后,HL患者和幸存者表现出持续的染色体不稳定,包括非克隆染色体畸变。染色体异常的频率和类型似乎取决于治疗的类型和所检查的细胞类型。例如,MOPP化疗会影响造血和生殖干细胞,导致长期基因毒性作用和无精子症,而ABVD化疗会影响瞬时精子细胞,大多数患者表现出精子发生的恢复。这两种方案对体细胞都有长期影响,在一小部分非癌细胞中呈现非克隆染色体畸变和基因组混乱。这是核型异质性的来源,最终可能产生更稳定的群体,获得克隆染色体畸变并导致新癌症的发展。