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; Koichi Takahashi

doi:10.1038/s41467-020-19119-8

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. DiNardoFarhad 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^*, Koichi Takahashi^*

^*Corresponding author for this work

Surgery, Thoracic Surgery Division

Research output: Contribution to journal › Article › peer-review

200 Scopus citations

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.

Original language	English (US)
Article number	5327
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19119-8
State	Published - Dec 1 2020

Funding

This study was supported in part by the Cancer Prevention and Research Institute of Texas (grant R120501 to P.A.F.), the Welch Foundation (grant G-0040 to P.A.F.), the University of Texas System STARS Award (grant PS100149 to P.A.F.), Physician Scientist Program at MD Anderson (to K.T.), the Leukemia and Lymphoma Society (NIH CA193235) (to D.N.), Lyda Hill Foundation (to P.A.F.), the Charif Souki Cancer Research Fund (to H.K.), the MD Anderson Cancer Center Leukemia SPORE grant (NIH P50 CA100632) (to H.K.), the MD Anderson Cancer Center Support Grant (NIH/NCI P30 CA016672), S10 shared instrumentation grant for NovaSeq 6000 (NIH 1S10OD024977-01), Leukemia Research Fund (to K.M.), Japan Society for the Promotion of Science Research Fellowships for Young Scientists (to K.M.), Japan Society for the Promotion of Science Overseas Research Fellowships (to T.T.), and generous philanthropic contributions to MD Anderson’s Moon Shot Program (to P.A.F., K.T., G.G.M., and H.K.). We thank Amy Ninetto at Department of Scientific Publications at MD Anderson for providing scientific editing of the manuscript. We also thank Charles Silver, Dennis Eastburn, Robert Durruthy–Durruthy, Matt Cato, Hannah Viernes, Anup Parikh, Sombeet Sahu, Kelly Kaihara, and all others members of Mission Bio Inc. for the technical support.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

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Morita, K., Wang, F., Jahn, K., Hu, T., Tanaka, T., Sasaki, Y., Kuipers, J., Loghavi, S., Wang, S. A., Yan, Y., Furudate, K., Matthews, J., Little, L., Gumbs, C., Zhang, J., Song, X., Thompson, E., Patel, K. P., Bueso-Ramos, C. E., ... Takahashi, K. (2020). Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics. Nature communications, 11(1), Article 5327. https://doi.org/10.1038/s41467-020-19119-8

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title = "Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics",

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.",

author = "Kiyomi Morita and Feng Wang and Katharina Jahn and Tianyuan Hu and Tomoyuki Tanaka and Yuya Sasaki and Jack Kuipers and Sanam Loghavi and Wang, {Sa A.} and Yuanqing Yan and Ken Furudate and Jairo Matthews and Latasha Little and Curtis Gumbs and Jianhua Zhang and Xingzhi Song and Erika Thompson and Patel, {Keyur P.} and Bueso-Ramos, {Carlos E.} and DiNardo, {Courtney D.} and Farhad Ravandi and Elias Jabbour and Michael Andreeff and Jorge Cortes and Kapil Bhalla and Guillermo Garcia-Manero and Hagop Kantarjian and Marina Konopleva and Daisuke Nakada and Nicholas Navin and Niko Beerenwinkel and Futreal, {P. Andrew} and Koichi Takahashi",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

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doi = "10.1038/s41467-020-19119-8",

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Morita, K, Wang, F, Jahn, K, Hu, T, Tanaka, T, Sasaki, Y, Kuipers, J, Loghavi, S, Wang, SA, Yan, Y, Furudate, K, Matthews, J, Little, L, Gumbs, C, Zhang, J, Song, X, Thompson, E, Patel, KP, Bueso-Ramos, CE, DiNardo, CD, Ravandi, F, Jabbour, E, Andreeff, M, Cortes, J, Bhalla, K, Garcia-Manero, G, Kantarjian, H, Konopleva, M, Nakada, D, Navin, N, Beerenwinkel, N, Futreal, PA & Takahashi, K 2020, 'Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics', Nature communications, vol. 11, no. 1, 5327. https://doi.org/10.1038/s41467-020-19119-8

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AU - Morita, Kiyomi

AU - Wang, Feng

AU - Jahn, Katharina

AU - Hu, Tianyuan

AU - Tanaka, Tomoyuki

AU - Sasaki, Yuya

AU - Kuipers, Jack

AU - Loghavi, Sanam

AU - Wang, Sa A.

AU - Yan, Yuanqing

AU - Furudate, Ken

AU - Matthews, Jairo

AU - Little, Latasha

AU - Gumbs, Curtis

AU - Zhang, Jianhua

AU - Song, Xingzhi

AU - Thompson, Erika

AU - Patel, Keyur P.

AU - Bueso-Ramos, Carlos E.

AU - DiNardo, Courtney D.

AU - Ravandi, Farhad

AU - Jabbour, Elias

AU - Andreeff, Michael

AU - Cortes, Jorge

AU - Bhalla, Kapil

AU - Garcia-Manero, Guillermo

AU - Kantarjian, Hagop

AU - Konopleva, Marina

AU - Nakada, Daisuke

AU - Navin, Nicholas

AU - Beerenwinkel, Niko

AU - Futreal, P. Andrew

AU - Takahashi, Koichi

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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JF - Nature communications

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ER -

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

Abstract

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UN SDGs

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