title: Clonal dynamics in a single AML case tracked for 9 years reveals the complexity of leukemia progression.
abstract: Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to undergo substantial clonal evolution over the course of the disease. AML tends to harbor fewer mutations than solid tumors, making it challenging to infer clonal structure. Here, we present a 9-year, whole-exome sequencing study of a single case at 12 time points, from the initial diagnosis until a fourth relapse, including 6 remission samples in between. To the best of our knowledge, it covers the longest time span of any data set of its kind. We used these time series data to track the hierarchy and order of variant acquisition, and subsequently analyzed the evolution of somatic variants to infer clonal structure. From this, we postulate the development and extinction of subclones, as well as their anticorrelated expansion via varying drug responses. In particular, we show that new subclones started appearing after the first complete remission. The presence and absence of different subclones during remission and relapses implies differing drug responses among subclones. Our study shows that time series analysis contrasting remission and relapse periods provides a much more comprehensive view of clonal structure and evolution.
authors.affiliation: Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.|The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Pathology and Tumour Biology, Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.affiliation: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.|The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Tyndel
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: J-S
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: D-H
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Hematology, Cancer Research Institute, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, Republic of Korea.
authors.forename: G
authors.initials: G
authors.lastname: Kong
authors.affiliation: Department of Pathology and Tumour Biology, Kyoto University, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.|The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Hematopoietic Genomics Research Centre, Chonnam National University, Hwasun, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D D
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000328:Adult; D060965:Clonal Evolution; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D012008:Recurrence