Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics

Kiyomi Morita, Feng Wang, Katharina Jahn, Tianyuan Hu, Tomoyuki Tanaka, Yuya Sasaki, Jack Kuipers, Sanam Loghavi, Sa A. Wang, Yuanqing Yan, Ken Furudate, Jairo Matthews, Latasha Little, Curtis Gumbs, Jianhua Zhang, Xingzhi Song, Erika Thompson, Keyur P. Patel, Carlos E. Bueso-Ramos, Courtney D. DiNardo, Farhad Ravandi, Elias Jabbour, Michael Andreeff, Jorge Cortes, Kapil Bhalla, Guillermo Garcia-Manero, Hagop Kantarjian, Marina Konopleva, Daisuke Nakada, Nicholas Navin, Niko Beerenwinkel (), P. Andrew Futreal () and Koichi Takahashi ()
Additional contact information
Kiyomi Morita: The University of Texas MD Anderson Cancer Center
Feng Wang: The University of Texas MD Anderson Cancer Center
Katharina Jahn: ETH Zurich
Tianyuan Hu: Baylor College of Medicine
Tomoyuki Tanaka: The University of Texas MD Anderson Cancer Center
Yuya Sasaki: The University of Texas MD Anderson Cancer Center
Jack Kuipers: ETH Zurich
Sanam Loghavi: The University of Texas MD Anderson Cancer Center
Sa A. Wang: The University of Texas MD Anderson Cancer Center
Yuanqing Yan: The University of Texas Health Science Center at Houston
Ken Furudate: The University of Texas MD Anderson Cancer Center
Jairo Matthews: The University of Texas MD Anderson Cancer Center
Latasha Little: The University of Texas MD Anderson Cancer Center
Curtis Gumbs: The University of Texas MD Anderson Cancer Center
Jianhua Zhang: The University of Texas MD Anderson Cancer Center
Xingzhi Song: The University of Texas MD Anderson Cancer Center
Erika Thompson: The University of Texas MD Anderson Cancer Center
Keyur P. Patel: The University of Texas MD Anderson Cancer Center
Carlos E. Bueso-Ramos: The University of Texas MD Anderson Cancer Center
Courtney D. DiNardo: The University of Texas MD Anderson Cancer Center
Farhad Ravandi: The University of Texas MD Anderson Cancer Center
Elias Jabbour: The University of Texas MD Anderson Cancer Center
Michael Andreeff: The University of Texas MD Anderson Cancer Center
Jorge Cortes: The University of Texas MD Anderson Cancer Center
Kapil Bhalla: The University of Texas MD Anderson Cancer Center
Guillermo Garcia-Manero: The University of Texas MD Anderson Cancer Center
Hagop Kantarjian: The University of Texas MD Anderson Cancer Center
Marina Konopleva: The University of Texas MD Anderson Cancer Center
Daisuke Nakada: The University of Texas MD Anderson Cancer Center
Nicholas Navin: The University of Texas MD Anderson Cancer Center
Niko Beerenwinkel: ETH Zurich
P. Andrew Futreal: The University of Texas MD Anderson Cancer Center
Koichi Takahashi: The University of Texas MD Anderson Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Clonal diversity is a consequence of cancer cell evolution driven by Darwinian selection. Precise characterization of clonal architecture is essential to understand the evolutionary history of tumor development and its association with treatment resistance. Here, using a single-cell DNA sequencing, we report the clonal architecture and mutational histories of 123 acute myeloid leukemia (AML) patients. The single-cell data reveals cell-level mutation co-occurrence and enables reconstruction of mutational histories characterized by linear and branching patterns of clonal evolution, with the latter including convergent evolution. Through xenotransplantion, we show leukemia initiating capabilities of individual subclones evolving in parallel. Also, by simultaneous single-cell DNA and cell surface protein analysis, we illustrate both genetic and phenotypic evolution in AML. Lastly, single-cell analysis of longitudinal samples reveals underlying evolutionary process of therapeutic resistance. Together, these data unravel clonal diversity and evolution patterns of AML, and highlight their clinical relevance in the era of precision medicine.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19119-8

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DOI: 10.1038/s41467-020-19119-8

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