dc.contributor.author | Oliveira, Tiago | |
dc.contributor.author | Zhang, Mingfeng | |
dc.contributor.author | Joo, Eun Ji | |
dc.contributor.author | Abdel-Azim, Hisham | |
dc.contributor.author | Chen, Chun-Wei | |
dc.contributor.author | Yang, Lu | |
dc.contributor.author | Chou, Chih-Hsing | |
dc.contributor.author | Qin, Xi | |
dc.contributor.author | Chen, Jianjun | |
dc.contributor.author | Alagesan, Kathirvel | |
dc.contributor.author | Almeida, Andreia | |
dc.contributor.author | Jacob, Francis | |
dc.contributor.author | Packer, Nicolle H | |
dc.contributor.author | von Itzstein, Mark | |
dc.contributor.author | Heisterkamp, Nora | |
dc.contributor.author | Kolarich, Daniel | |
dc.date.accessioned | 2021-10-19T23:59:40Z | |
dc.date.available | 2021-10-19T23:59:40Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1838-7640 | |
dc.identifier.doi | 10.7150/thno.65398 | |
dc.identifier.uri | http://hdl.handle.net/10072/409298 | |
dc.description.abstract | B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed-lineage leukemia gene rearrangement (MLL-r) is a poor-prognosis subtype for which additional therapeutic targets are urgently needed. Currently no multi-omics data set for primary MLL r patient cells exists that integrates transcriptomics, proteomics and glycomics to gain an inclusive picture of theranostic targets. Methods: We have integrated transcriptomics, proteomics and glycomics to i) obtain the first inclusive picture of primary patient BCP-ALL cells and identify molecular signatures that distinguish leukemic from normal precursor B-cells and ii) better understand the benefits and limitations of the applied technologies to deliver deep molecular sequence data across major cellular biopolymers. Results: MLL-r cells feature an extensive remodeling of their glycocalyx, with increased levels of Core 2-type O-glycans and complex N-glycans as well as significant changes in sialylation and fucosylation. Notably, glycosaminoglycan remodeling from chondroitin sulfate to heparan sulfate was observed. A survival screen, to determine if glycan remodeling enzymes are redundant, identified MGAT1 and NGLY1, essential components of the N-glycosylation/degradation pathway, as highly relevant within this in vitro screening. OGT and OGA, unique enzymes that regulate intracellular O-GlcNAcylation, were also indispensable. Transcriptomics and proteomics further identified Fes and GALNT7-mediated glycosylation as possible therapeutic targets. While there is overall good correlation between transcriptomics and proteomics data, we demonstrate that a systematic combined multi-omics approach delivers important diagnostic information that is missed when applying a single omics technology. Conclusions: Apart from confirming well-known MLL-r BCP-ALL glycoprotein markers, our integrated multi-omics workflow discovered previously unidentified diagnostic/therapeutic protein targets. | |
dc.description.peerreviewed | Yes | |
dc.language | eng | |
dc.publisher | Ivyspring International Publisher | |
dc.relation.ispartofpagefrom | 9519 | |
dc.relation.ispartofpageto | 9537 | |
dc.relation.ispartofissue | 19 | |
dc.relation.ispartofjournal | Theranostics | |
dc.relation.ispartofvolume | 11 | |
dc.subject.fieldofresearch | Glycobiology | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearch | Glycoconjugates | |
dc.subject.fieldofresearch | Proteomics and intermolecular interactions (excl. medical proteomics) | |
dc.subject.fieldofresearch | Medical biochemistry - proteins and peptides (incl. medical proteomics) | |
dc.subject.fieldofresearch | Analytical biochemistry | |
dc.subject.fieldofresearch | Genomics and transcriptomics | |
dc.subject.fieldofresearch | Cancer diagnosis | |
dc.subject.fieldofresearch | Paediatrics not elsewhere classified | |
dc.subject.fieldofresearchcode | 310107 | |
dc.subject.fieldofresearchcode | 3211 | |
dc.subject.fieldofresearchcode | 340405 | |
dc.subject.fieldofresearchcode | 310109 | |
dc.subject.fieldofresearchcode | 320506 | |
dc.subject.fieldofresearchcode | 310101 | |
dc.subject.fieldofresearchcode | 310204 | |
dc.subject.fieldofresearchcode | 321102 | |
dc.subject.fieldofresearchcode | 321399 | |
dc.subject.keywords | Glycomics | |
dc.subject.keywords | Leukemia | |
dc.subject.keywords | Proteomics | |
dc.subject.keywords | Transcriptomics | |
dc.subject.keywords | multi-omics | |
dc.title | Glycoproteome remodeling in MLL-rearranged B-cell precursor acute lymphoblastic leukemia | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Oliveira, T; Zhang, M; Joo, EJ; Abdel-Azim, H; Chen, C-W; Yang, L; Chou, C-H; Qin, X; Chen, J; Alagesan, K; Almeida, A; Jacob, F; Packer, NH; von Itzstein, M; Heisterkamp, N; Kolarich, D, Glycoproteome remodeling in MLL-rearranged B-cell precursor acute lymphoblastic leukemia., Theranostics, 2021, 11 (19), pp. 9519-9537 | |
dcterms.dateAccepted | 2021-09-03 | |
dcterms.license | https://creativecommons.org/licenses/by/4.0/ | |
dc.date.updated | 2021-10-18T00:56:19Z | |
dc.description.version | Version of Record (VoR) | |
gro.rights.copyright | © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Kolarich, Daniel | |
gro.griffith.author | von Itzstein, Mark | |
gro.griffith.author | Packer, Nicki | |