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Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia

Author

Listed:
  • Carmen D. Herling

    (University of Cologne)

  • Nima Abedpour

    (University of Cologne
    University of Cologne)

  • Jonathan Weiss

    (University of Cologne)

  • Anna Schmitt

    (University of Cologne
    University of Cologne
    University of Cologne)

  • Ron Daniel Jachimowicz

    (University of Cologne
    University of Cologne
    University of Cologne)

  • Olaf Merkel

    (University of Cologne
    University of Cologne)

  • Maria Cartolano

    (University of Cologne
    University of Cologne)

  • Sebastian Oberbeck

    (University of Cologne
    University of Cologne
    University of Cologne
    University of Cologne)

  • Petra Mayer

    (University of Cologne
    University of Cologne
    University of Cologne
    University of Cologne)

  • Valeska Berg

    (University of Cologne
    University of Cologne)

  • Daniel Thomalla

    (University of Cologne
    University of Cologne)

  • Nadine Kutsch

    (University of Cologne)

  • Marius Stiefelhagen

    (University of Cologne)

  • Paula Cramer

    (University of Cologne)

  • Clemens-Martin Wendtner

    (Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing)

  • Thorsten Persigehl

    (Cologne University Hospital)

  • Andreas Saleh

    (Städtisches Klinikum München Schwabing)

  • Janine Altmüller

    (University of Cologne
    University of Cologne)

  • Peter Nürnberg

    (University of Cologne
    University of Cologne
    University of Cologne)

  • Christian Pallasch

    (University of Cologne
    University of Cologne
    University of Cologne)

  • Viktor Achter

    (University of Cologne)

  • Ulrich Lang

    (University of Cologne
    University of Cologne)

  • Barbara Eichhorst

    (University of Cologne)

  • Roberta Castiglione

    (University of Cologne)

  • Stephan C. Schäfer

    (University of Cologne)

  • Reinhard Büttner

    (University of Cologne)

  • Karl-Anton Kreuzer

    (University of Cologne)

  • Hans Christian Reinhardt

    (University of Cologne
    University of Cologne
    University of Cologne)

  • Michael Hallek

    (University of Cologne
    University of Cologne
    University of Cologne)

  • Lukas P. Frenzel

    (University of Cologne
    University of Cologne)

  • Martin Peifer

    (University of Cologne
    University of Cologne)

Abstract

Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions.

Suggested Citation

  • Carmen D. Herling & Nima Abedpour & Jonathan Weiss & Anna Schmitt & Ron Daniel Jachimowicz & Olaf Merkel & Maria Cartolano & Sebastian Oberbeck & Petra Mayer & Valeska Berg & Daniel Thomalla & Nadine , 2018. "Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03170-7
    DOI: 10.1038/s41467-018-03170-7
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    Cited by:

    1. Othman Al-Sawaf & Can Zhang & Hyun Yong Jin & Sandra Robrecht & Yoonha Choi & Sandhya Balasubramanian & Alex Kotak & Yi Meng Chang & Anna Maria Fink & Eugen Tausch & Christof Schneider & Matthias Ritg, 2023. "Transcriptomic profiles and 5-year results from the randomized CLL14 study of venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab in chronic lymphocytic leukemia," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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