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Bone marrow derived stromal cells from myelodysplastic syndromes are altered but not clonally mutated in vivo

Author

Listed:
  • Johann-Christoph Jann

    (Medical Faculty Mannheim of the Heidelberg University)

  • Maximilian Mossner

    (Medical Faculty Mannheim of the Heidelberg University)

  • Vladimir Riabov

    (Medical Faculty Mannheim of the Heidelberg University)

  • Eva Altrock

    (Medical Faculty Mannheim of the Heidelberg University)

  • Nanni Schmitt

    (Medical Faculty Mannheim of the Heidelberg University)

  • Johanna Flach

    (Medical Faculty Mannheim of the Heidelberg University)

  • Qingyu Xu

    (Medical Faculty Mannheim of the Heidelberg University)

  • Verena Nowak

    (Medical Faculty Mannheim of the Heidelberg University)

  • Julia Obländer

    (Medical Faculty Mannheim of the Heidelberg University)

  • Iris Palme

    (Medical Faculty Mannheim of the Heidelberg University)

  • Nadine Weimer

    (Medical Faculty Mannheim of the Heidelberg University)

  • Alexander Streuer

    (Medical Faculty Mannheim of the Heidelberg University)

  • Ahmed Jawhar

    (Medical Faculty Mannheim of the Heidelberg University)

  • Ali Darwich

    (Medical Faculty Mannheim of the Heidelberg University)

  • Mohammad Jawhar

    (Medical Faculty Mannheim of the Heidelberg University)

  • Georgia Metzgeroth

    (Medical Faculty Mannheim of the Heidelberg University)

  • Florian Nolte

    (Medical Faculty Mannheim of the Heidelberg University)

  • Wolf-Karsten Hofmann

    (Medical Faculty Mannheim of the Heidelberg University)

  • Daniel Nowak

    (Medical Faculty Mannheim of the Heidelberg University)

Abstract

The bone marrow (BM) stroma in myeloid neoplasms is altered and it is hypothesized that this cell compartment may also harbor clonal somatically acquired mutations. By exome sequencing of in vitro expanded mesenchymal stromal cells (MSCs) from n = 98 patients with myelodysplastic syndrome (MDS) and n = 28 healthy controls we show that these cells accumulate recurrent mutations in genes such as ZFX (n = 8/98), RANK (n = 5/98), and others. MDS derived MSCs display higher mutational burdens, increased replicative stress, senescence, inflammatory gene expression, and distinct mutational signatures as compared to healthy MSCs. However, validation experiments in serial culture passages, chronological BM aspirations and backtracking of high confidence mutations by re-sequencing primary sorted MDS MSCs indicate that the discovered mutations are secondary to in vitro expansion but not present in primary BM. Thus, we here report that there is no evidence for clonal mutations in the BM stroma of MDS patients.

Suggested Citation

  • Johann-Christoph Jann & Maximilian Mossner & Vladimir Riabov & Eva Altrock & Nanni Schmitt & Johanna Flach & Qingyu Xu & Verena Nowak & Julia Obländer & Iris Palme & Nadine Weimer & Alexander Streuer , 2021. "Bone marrow derived stromal cells from myelodysplastic syndromes are altered but not clonally mutated in vivo," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26424-3
    DOI: 10.1038/s41467-021-26424-3
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    1. Ewart Kuijk & Myrthe Jager & Bastiaan Roest & Mauro D. Locati & Arne Hoeck & Jerome Korzelius & Roel Janssen & Nicolle Besselink & Sander Boymans & Ruben Boxtel & Edwin Cuppen, 2020. "Publisher Correction: The mutational impact of culturing human pluripotent and adult stem cells," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
    2. Yaopan Mao & Anna Kuta & Ivan Crespo-Enriquez & Danielle Whiting & Tina Martin & Joanna Mulvaney & Kenneth D. Irvine & Philippa Francis-West, 2016. "Dchs1–Fat4 regulation of polarized cell behaviours during skeletal morphogenesis," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    3. Francesco Maura & Andrea Degasperi & Ferran Nadeu & Daniel Leongamornlert & Helen Davies & Luiza Moore & Romina Royo & Bachisio Ziccheddu & Xose S. Puente & Herve Avet-Loiseau & Peter J. Campbell & Se, 2019. "Author Correction: A practical guide for mutational signature analysis in hematological malignancies," Nature Communications, Nature, vol. 10(1), pages 1-1, December.
    4. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Correction: Corrigendum: Signatures of mutational processes in human cancer," Nature, Nature, vol. 502(7470), pages 258-258, October.
    5. Michael S. Lawrence & Petar Stojanov & Paz Polak & Gregory V. Kryukov & Kristian Cibulskis & Andrey Sivachenko & Scott L. Carter & Chip Stewart & Craig H. Mermel & Steven A. Roberts & Adam Kiezun & Pe, 2013. "Mutational heterogeneity in cancer and the search for new cancer-associated genes," Nature, Nature, vol. 499(7457), pages 214-218, July.
    6. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Signatures of mutational processes in human cancer," Nature, Nature, vol. 500(7463), pages 415-421, August.
    7. Lei Dong & Wen-Mei Yu & Hong Zheng & Mignon L. Loh & Silvia T. Bunting & Melinda Pauly & Gang Huang & Muxiang Zhou & Hal E. Broxmeyer & David T. Scadden & Cheng-Kui Qu, 2016. "Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment," Nature, Nature, vol. 539(7628), pages 304-308, November.
    8. Ewart Kuijk & Myrthe Jager & Bastiaan Roest & Mauro D. Locati & Arne Hoeck & Jerome Korzelius & Roel Janssen & Nicolle Besselink & Sander Boymans & Ruben Boxtel & Edwin Cuppen, 2020. "The mutational impact of culturing human pluripotent and adult stem cells," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    9. Francesco Maura & Andrea Degasperi & Ferran Nadeu & Daniel Leongamornlert & Helen Davies & Luiza Moore & Romina Royo & Bachisio Ziccheddu & Xose S. Puente & Herve Avet-Loiseau & Peter J. Campbell & Se, 2019. "A practical guide for mutational signature analysis in hematological malignancies," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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    1. Qingyu Xu & Alexander Streuer & Johann-Christoph Jann & Eva Altrock & Nanni Schmitt & Johanna Flach & Carla Sens-Albert & Felicitas Rapp & Julia Wolf & Verena Nowak & Nadine Weimer & Julia Obländer & , 2023. "Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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