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

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, Ahmed Jawhar, Ali Darwich, Mohammad Jawhar, Georgia Metzgeroth, Florian Nolte, Wolf-Karsten Hofmann and Daniel Nowak ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26424-3

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