Germline mutations: many roles in leukemogenesis

• Type of Material: Article
• Authors: Kevin Z Chen, Emory University; Rafi Kazi, Emory University; Christopher Porter, Emory University; Cheng-Kui Qu, Emory University
• Language: English
• Date: 2020-07-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Wolters Kluwer Health, Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/MOH.0000000000000596
• Title of Journal or Parent Work: CURRENT OPINION IN HEMATOLOGY
• Volume: 27
• Issue: 4
• Start Page: 288
• End Page: 293
• Grant/Funding Information: This work was supported by the National Institutes of Health grant HL130995 (to C.K.Q.).
• Keywords: CLONAL HEMATOPOIESIS; TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; BONE-MARROW NICHE; leukemogenesis; DISEASE; antitumor immunity; SURVIVAL; hematopoietic stem cell; germline mutations; TET2; CORRELATE; Hematology; STEM-CELLS; microenvironment; MANAGEMENT; Science & Technology; Life Sciences & Biomedicine; clonal hematopoiesis of indeterminate potential

Abstract

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.