Germline mutations: many roles in leukemogenesis.

PURPOSE OF REVIEW The purpose of this review is to summarize the current understanding of germline mutations as they contribute to leukemia development and progression. We also discuss how these new insights may help improve clinical management of germline mutations associated with leukemia. RECENT FINDINGS Germline mutations may represent important initial mutations in the development of leukemia where interaction with somatic mutations provide further hits in leukemic progression. In addition, germline mutations may also contribute to leukemogenesis by impacting bone marrow stem-cell microenvironment and immune cell development and function. SUMMARY Leukemia is characterized by the clonal expansion of malignant cells secondary to somatic or germline mutations in a variety of genes. Understanding somatic mutations that drive leukemogenesis has drastically improved our knowledge of leukemia biology and led to novel therapeutic strategies. Advances have also been made in identifying germline mutations that may affect leukemic development and progression. This review will discuss the biological and clinical relationship of germline mutations with clonal hematopoiesis, bone marrow microenvironment, and immunity in the progression of leukemia.

综述目的 本综述的目的是总结目前对种系突变在白血病发生和发展中作用的理解。我们还讨论了这些新的见解如何有助于改善与白血病相关的种系突变的临床管理。 近期发现 种系突变可能是白血病发生过程中重要的起始突变，其与体细胞突变的相互作用在白血病进展中进一步产生影响。此外，种系突变还可能通过影响骨髓干细胞微环境以及免疫细胞的发育和功能而促进白血病的发生。 总结 白血病的特征是多种基因的体细胞或种系突变导致恶性细胞的克隆性增殖。对驱动白血病发生的体细胞突变的理解极大地提高了我们对白血病生物学的认识，并催生了新的治疗策略。在识别可能影响白血病发生和发展的种系突变方面也取得了进展。本综述将讨论种系突变与克隆性造血、骨髓微环境以及白血病进展过程中的免疫之间的生物学和临床关系。