Therapy-selected clonal hematopoiesis and its role in myeloid neoplasms. (March 2023) - Jahn, Jacob
Abstract: Therapy-related myeloid neoplasms (t-MN) account for approximately 10–15% of all myeloid neoplasms and are associated with poor prognosis. Genomic characterization of t-MN to date has been limited in comparison to the considerable sequencing efforts performed for de novo myeloid neoplasms. Until recently, targeted deep sequencing (TDS) or whole exome sequencing (WES) have been the primary technologies utilized and thus limited the ability to explore the landscape of structural variants and mutational signatures. In the past decade, population-level studies have identified clonal hematopoiesis as a risk factor for the development of myeloid neoplasms. However, emerging research on clonal hematopoiesis as a risk factor for developing t-MN is evolving, and much is unknown about the progression of CH to t-MN. In this work, we will review the current knowledge of the genomic landscape of t-MN, discuss background knowledge of clonal hematopoiesis gained from studies of de novo myeloid neoplasms, and examine the recent literature studying the role of therapeutic selection of CH and its evolution under the effects of antineoplastic therapy. Finally, we will discuss the potential implications on current clinical practice and the areas of focus needed for future research into therapy-selected clonal hematopoiesis in myeloid neoplasms. Graphical Abstract: ga1 Highlights: Therapy related myeloid neoplasms (t-MN) make up 10–20% of myeloid malignancies Clonal hematopoiesis (CH) occurs at high frequency in t-MN Whole genome sequencing characterizes complexity of t-MN genetic alterations Triad of CH, chemotherapy selection and immune response contributes to t-MN