Show simple item record

dc.contributor.authorOliveira, Tiago
dc.contributor.authorZhang, Mingfeng
dc.contributor.authorJoo, Eun Ji
dc.contributor.authorAbdel-Azim, Hisham
dc.contributor.authorChen, Chun-Wei
dc.contributor.authorYang, Lu
dc.contributor.authorChou, Chih-Hsing
dc.contributor.authorQin, Xi
dc.contributor.authorChen, Jianjun
dc.contributor.authorAlagesan, Kathirvel
dc.contributor.authorAlmeida, Andreia
dc.contributor.authorJacob, Francis
dc.contributor.authorPacker, Nicolle H
dc.contributor.authorvon Itzstein, Mark
dc.contributor.authorHeisterkamp, Nora
dc.contributor.authorKolarich, Daniel
dc.date.accessioned2021-10-19T23:59:40Z
dc.date.available2021-10-19T23:59:40Z
dc.date.issued2021
dc.identifier.issn1838-7640
dc.identifier.doi10.7150/thno.65398
dc.identifier.urihttp://hdl.handle.net/10072/409298
dc.description.abstractB-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.peerreviewedYes
dc.languageeng
dc.publisherIvyspring International Publisher
dc.relation.ispartofpagefrom9519
dc.relation.ispartofpageto9537
dc.relation.ispartofissue19
dc.relation.ispartofjournalTheranostics
dc.relation.ispartofvolume11
dc.subject.fieldofresearchGlycobiology
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchGlycoconjugates
dc.subject.fieldofresearchProteomics and intermolecular interactions (excl. medical proteomics)
dc.subject.fieldofresearchMedical biochemistry - proteins and peptides (incl. medical proteomics)
dc.subject.fieldofresearchAnalytical biochemistry
dc.subject.fieldofresearchGenomics and transcriptomics
dc.subject.fieldofresearchCancer diagnosis
dc.subject.fieldofresearchPaediatrics not elsewhere classified
dc.subject.fieldofresearchcode310107
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode340405
dc.subject.fieldofresearchcode310109
dc.subject.fieldofresearchcode320506
dc.subject.fieldofresearchcode310101
dc.subject.fieldofresearchcode310204
dc.subject.fieldofresearchcode321102
dc.subject.fieldofresearchcode321399
dc.subject.keywordsGlycomics
dc.subject.keywordsLeukemia
dc.subject.keywordsProteomics
dc.subject.keywordsTranscriptomics
dc.subject.keywordsmulti-omics
dc.titleGlycoproteome remodeling in MLL-rearranged B-cell precursor acute lymphoblastic leukemia
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationOliveira, 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.dateAccepted2021-09-03
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-10-18T00:56:19Z
dc.description.versionVersion 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.hasfulltextFull Text
gro.griffith.authorKolarich, Daniel
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorPacker, Nicki
gro.griffith.authorOliveira, Tiago M.
gro.griffith.authorAlagesan, Kathirvel


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record