TY - JOUR
T1 - Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics
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
N1 - Funding Information:
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.
Publisher Copyright:
© 2020, The Author(s).
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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U2 - 10.1038/s41467-020-19119-8
DO - 10.1038/s41467-020-19119-8
M3 - Article
C2 - 33087716
AN - SCOPUS:85093070605
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5327
ER -