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Article

Time-Resolved scRNA-Seq Tracks the Adaptation of a Sensitive MCL Cell Line to Ibrutinib Treatment

1
Institute of Pathology, University of Würzburg and Comprehensive Cancer Center (CCC) Mainfranken, 97080 Würzburg, Germany
2
Helmholtz Institute for RNA-Based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), 97080 Würzburg, Germany
3
Core Unit Systems Medicine, University of Würzburg, 97080 Würzburg, Germany
4
Mildred Scheel Early Career Center (MSNZ), University Hospital of Würzburg, 97080 Würzburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Pavel Sumazin
Int. J. Mol. Sci. 2021, 22(5), 2276; https://doi.org/10.3390/ijms22052276
Received: 15 January 2021 / Revised: 16 February 2021 / Accepted: 23 February 2021 / Published: 25 February 2021
(This article belongs to the Special Issue Molecular Genetics of Tumor Heterogeneity)
Since the approval of ibrutinib for relapsed/refractory mantle cell lymphoma (MCL), the treatment of this rare mature B-cell neoplasm has taken a great leap forward. Despite promising efficacy of the Bruton tyrosine kinase inhibitor, resistance arises inevitably and the underlying mechanisms remain to be elucidated. Here, we aimed to decipher the response of a sensitive MCL cell line treated with ibrutinib using time-resolved single-cell RNA sequencing. The analysis uncovered five subpopulations and their individual responses to the treatment. The effects on the B cell receptor pathway, cell cycle, surface antigen expression, and metabolism were revealed by the computational analysis and were validated by molecular biological methods. The observed upregulation of B cell receptor signaling, crosstalk with the microenvironment, upregulation of CD52, and metabolic reprogramming towards dependence on oxidative phosphorylation favor resistance to ibrutinib treatment. Targeting these cellular responses provide new therapy options in MCL. View Full-Text
Keywords: mantle cell lymphoma; scRNA-seq; ibrutinib; drug resistance mantle cell lymphoma; scRNA-seq; ibrutinib; drug resistance
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MDPI and ACS Style

Fuhr, V.; Vafadarnejad, E.; Dietrich, O.; Arampatzi, P.; Riedel, A.; Saliba, A.-E.; Rosenwald, A.; Rauert-Wunderlich, H. Time-Resolved scRNA-Seq Tracks the Adaptation of a Sensitive MCL Cell Line to Ibrutinib Treatment. Int. J. Mol. Sci. 2021, 22, 2276. https://doi.org/10.3390/ijms22052276

AMA Style

Fuhr V, Vafadarnejad E, Dietrich O, Arampatzi P, Riedel A, Saliba A-E, Rosenwald A, Rauert-Wunderlich H. Time-Resolved scRNA-Seq Tracks the Adaptation of a Sensitive MCL Cell Line to Ibrutinib Treatment. International Journal of Molecular Sciences. 2021; 22(5):2276. https://doi.org/10.3390/ijms22052276

Chicago/Turabian Style

Fuhr, Viktoria, Ehsan Vafadarnejad, Oliver Dietrich, Panagiota Arampatzi, Angela Riedel, Antoine-Emmanuel Saliba, Andreas Rosenwald, and Hilka Rauert-Wunderlich. 2021. "Time-Resolved scRNA-Seq Tracks the Adaptation of a Sensitive MCL Cell Line to Ibrutinib Treatment" International Journal of Molecular Sciences 22, no. 5: 2276. https://doi.org/10.3390/ijms22052276

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