Cardesa-Salzmann T M, Simon A, Graf N
Department of Pediatric Hematology and Oncology, Universitätsklinikum des Saarlandes, Homburg, Saarland, Germany.
Discov Oncol. 2022 Jan 10;13(1):5. doi: 10.1007/s12672-022-00465-6.
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer with precursor B-cell ALL (pB-ALL) accounting for ~ 85% of the cases. Childhood pB-ALL development is influenced by genetic susceptibility and host immune responses. The role of the intestinal microbiome in leukemogenesis is gaining increasing attention since Vicente-Dueñas' seminal work demonstrated that the gut microbiome is distinct in mice genetically predisposed to ALL and that the alteration of this microbiome by antibiotics is able to trigger pB-ALL in Pax5 heterozygous mice in the absence of infectious stimuli. In this review we provide an overview on novel insights on the role of the microbiome in normal and preleukemic hematopoiesis, inflammation, the effect of dysbiosis on hematopoietic stem cells and the emerging importance of the innate immune responses in the conversion from preleukemic to leukemic state in childhood ALL. Since antibiotics, which represent one of the most widely used medical interventions, alter the gut microbial composition and can cause a state of dysbiosis, this raises exciting epidemiological questions regarding the implications for antibiotic use in early life, especially in infants with a a preleukemic "first hit". Sheading light through a rigorous study on this piece of the puzzle may have broad implications for clinical practice.
急性淋巴细胞白血病（ALL）是最常见的儿童癌症，其中前体B细胞ALL（pB-ALL）约占病例的85%。儿童pB-ALL的发生受遗传易感性和宿主免疫反应的影响。自比森特-杜埃尼亚斯的开创性研究表明，在遗传易患ALL的小鼠中肠道微生物群不同，并且抗生素对这种微生物群的改变能够在没有感染刺激的情况下在Pax5杂合小鼠中引发pB-ALL以来，肠道微生物群在白血病发生中的作用越来越受到关注。在这篇综述中，我们概述了微生物群在正常和白血病前期造血、炎症、生态失调对造血干细胞的影响以及先天免疫反应在儿童ALL从白血病前期向白血病状态转变中的新出现的重要性方面的新见解。由于抗生素是最广泛使用的医疗干预措施之一，会改变肠道微生物组成并可能导致生态失调状态，这就引发了关于早期生命中抗生素使用的影响的令人兴奋的流行病学问题，特别是对于有白血病前期“首次打击”的婴儿。通过对这一难题的严格研究来阐明情况可能对临床实践有广泛影响。
