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  Integrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures.

Schroeder, M. P., Bastian, L., Eckert, C., Gökbuget, N., James, A. R., Ortiz Tanchez, J., et al. (2019). Integrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures. Scientific Reports, 9(1): 4188. doi:10.1038/s41598-019-40786-1.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-2B59-A Version Permalink: http://hdl.handle.net/21.11116/0000-0003-2B60-1
Genre: Journal Article

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 Creators:
Schroeder, M. P., Author
Bastian, L., Author
Eckert, C., Author
Gökbuget, N., Author
James, A. R., Author
Ortiz Tanchez, J., Author
Schlee, C., Author
Isaakidis, K., Author
Häupl, B., Author
Baum, K., Author
Lozano, O. A. M., Author
Kouidri, K., Author
Pan, K. T.1, Author              
Urlaub, H.1, Author              
Schwartz, S., Author
Burmeister, T., Author
von Stackelberg, A., Author
Hoelzer, D., Author
Pfeiffer, H., Author
Rieger, M. A., Author
Göllner, S., AuthorOellerich, T., AuthorHorstman, M., AuthorSchrappe, M., AuthorWolf, J., AuthorKirschner-Schwabe, R., AuthorBrüggemann, M., AuthorMüller-Tidow, C., AuthorServe, H., AuthorNeumann, M., AuthorBaldus, C. D., Author more..
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              

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 Abstract: Recent efforts reclassified B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) into more refined subtypes. Nevertheless, outcomes of relapsed BCP-ALL remain unsatisfactory, particularly in adult patients where the molecular basis of relapse is still poorly understood. To elucidate the evolution of relapse in BCP-ALL, we established a comprehensive multi-omics dataset including DNA-sequencing, RNA-sequencing, DNA methylation array and proteome MASS-spec data from matched diagnosis and relapse samples of BCP-ALL patients (n = 50) including the subtypes DUX4, Ph-like and two aneuploid subtypes. Relapse-specific alterations were enriched for chromatin modifiers, nucleotide and steroid metabolism including the novel candidates FPGS, AGBL and ZNF483. The proteome expression analysis unraveled deregulation of metabolic pathways at relapse including the key proteins G6PD, TKT, GPI and PGD. Moreover, we identified a novel relapse-specific gene signature specific for DUX4 BCP-ALL patients highlighting chemotaxis and cytokine environment as a possible driver event at relapse. This study presents novel insights at distinct molecular levels of relapsed BCP-ALL based on a comprehensive multi-omics integrated data set including a valuable proteomics data set. The relapse specific aberrations reveal metabolic signatures on genomic and proteomic levels in BCP-ALL relapse. Furthermore, the chemokine expression signature in DUX4 relapse underscores the distinct status of DUX4-fusion BCP-ALL.

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Language(s): eng - English
 Dates: 2019-03-12
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41598-019-40786-1
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Title: Scientific Reports
Source Genre: Journal
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Publ. Info: -
Pages: 11 Volume / Issue: 9 (1) Sequence Number: 4188 Start / End Page: - Identifier: -