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Clonal architecture predicts clinical outcomes and drug sensitivity in acute myeloid leukemia

Author

Listed:
  • Brooks A. Benard

    (Stanford University
    Stanford University)

  • Logan B. Leak

    (Stanford University
    Stanford University)

  • Armon Azizi

    (Stanford University)

  • Daniel Thomas

    (Stanford University
    University of Adelaide)

  • Andrew J. Gentles

    (Stanford University)

  • Ravindra Majeti

    (Stanford University)

Abstract

The impact of clonal heterogeneity on disease behavior or drug response in acute myeloid leukemia remains poorly understood. Using a cohort of 2,829 patients, we identify features of clonality associated with clinical features and drug sensitivities. High variant allele frequency for 7 mutations (including NRAS and TET2) associate with dismal prognosis; elevated GATA2 variant allele frequency correlates with better outcomes. Clinical features such as white blood cell count and blast percentage correlate with the subclonal abundance of mutations such as TP53 and IDH1. Furthermore, patients with cohesin mutations occurring before NPM1, or transcription factor mutations occurring before splicing factor mutations, show shorter survival. Surprisingly, a branched pattern of clonal evolution is associated with superior clinical outcomes. Finally, several mutations (including NRAS and IDH1) predict drug sensitivity based on their subclonal abundance. Together, these results demonstrate the importance of assessing clonal heterogeneity with implications for prognosis and actionable biomarkers for therapy.

Suggested Citation

  • Brooks A. Benard & Logan B. Leak & Armon Azizi & Daniel Thomas & Andrew J. Gentles & Ravindra Majeti, 2021. "Clonal architecture predicts clinical outcomes and drug sensitivity in acute myeloid leukemia," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27472-5
    DOI: 10.1038/s41467-021-27472-5
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    1. 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 & C, 2020. "Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Sagi Abelson & Grace Collord & Stanley W. K. Ng & Omer Weissbrod & Netta Mendelson Cohen & Elisabeth Niemeyer & Noam Barda & Philip C. Zuzarte & Lawrence Heisler & Yogi Sundaravadanam & Robert Luben &, 2018. "Prediction of acute myeloid leukaemia risk in healthy individuals," Nature, Nature, vol. 559(7714), pages 400-404, July.
    3. Jeffrey W. Tyner & Cristina E. Tognon & Daniel Bottomly & Beth Wilmot & Stephen E. Kurtz & Samantha L. Savage & Nicola Long & Anna Reister Schultz & Elie Traer & Melissa Abel & Anupriya Agarwal & Auro, 2018. "Functional genomic landscape of acute myeloid leukaemia," Nature, Nature, vol. 562(7728), pages 526-531, October.
    4. Min Zhang & Jin-Li Luo & Qianqian Sun & James Harber & Alan G. Dawson & Apostolos Nakas & Sara Busacca & Annabel J. Sharkey & David Waller & Michael T. Sheaff & Cathy Richards & Peter Wells-Jordan & A, 2021. "Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    5. Min Zhang & Jin-Li Luo & Qianqian Sun & James Harber & Alan G. Dawson & Apostolos Nakas & Sara Busacca & Annabel J. Sharkey & David Waller & Michael T. Sheaff & Cathy Richards & Peter Wells-Jordan & A, 2021. "Author Correction: Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment," Nature Communications, Nature, vol. 12(1), pages 1-1, December.
    6. Linde A. Miles & Robert L. Bowman & Tiffany R. Merlinsky & Isabelle S. Csete & Aik T. Ooi & Robert Durruthy-Durruthy & Michael Bowman & Christopher Famulare & Minal A. Patel & Pedro Mendez & Chrysanth, 2020. "Single-cell mutation analysis of clonal evolution in myeloid malignancies," Nature, Nature, vol. 587(7834), pages 477-482, November.
    7. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
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