Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Comprehensive Cancer Center Central Germany - Campus Jena, Universitätsklinikum Jena, Jena, Germany.
Institut für Humangenetik, Universitätsklinikum Jena, Jena, Germany.
Genes Immun. 2024 Aug;25(4):317-323. doi: 10.1038/s41435-024-00285-4. Epub 2024 Jul 9.
Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.
感染事件，如败血症和侵袭性真菌感染（IFD），对急性髓系白血病（AML）患者构成重大风险。以前的研究，包括我们自己的研究，表明先天免疫系统中单核苷酸多态性（SNPs）可能在影响个体感染易感性方面发挥作用。然而，这些关联中的许多在独立队列中缺乏验证。本研究旨在验证 6 个基因（TLR2、TLR4、Dectin-1、DC-SIGN、PTX3、L-Ficolin）中的 11 个候选 SNPs 在独立患者队列中的影响。对接受强化诱导化疗的新诊断 AML 患者的两个队列进行了分析：一个分层队列包含 186 例患者，一个验证队列包含 138 例患者。每个队列中的多个 SNPs 与感染并发症相关，特别是 DC-SIGN SNP rs4804800 在两个队列中均与败血症显著相关。PTX3 和 Dectin-1 基因中的 SNPs 分别与一个队列中的 IFD 发展相关。本研究代表了强化诱导化疗后 AML 患者感染相关候选基因的首次验证研究。确定感染的遗传易感性可能会对 AML 患者的抗菌预防和治疗管理产生重大影响。
