Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines.

Autor: Leo IR; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Aswad L; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Stahl M; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Kunold E; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Post F; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden.; Institute of Plant Biology and Biotechnology, University of Muenster, Schlossplatz 7, 48149, Muenster, Germany., Erkers T; Molecular Precision Medicine, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Struyf N; Molecular Precision Medicine, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Mermelekas G; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Joshi RN; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Gracia-Villacampa E; Division of Gene Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Östling P; Molecular Precision Medicine, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Kallioniemi OP; Molecular Precision Medicine, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Tamm KP; Department of Oncology-Pathology, Karolinska Institutet, J6:140 BioClinicum, Akademiska stråket 1, 171 64, Solna, Sweden., Siavelis I; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Lehtiö J; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Vesterlund M; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden., Jafari R; Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Tomtebodavägen 23A, 171 65, Solna, Sweden. rozbeh.jafari@ki.se.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Mar 30; Vol. 13 (1), pp. 1691. Date of Electronic Publication: 2022 Mar 30.
DOI: 10.1038/s41467-022-29224-5
Abstrakt: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although standard-of-care chemotherapeutics are sufficient for most ALL cases, there are subsets of patients with poor response who relapse in disease. The biology underlying differences between subtypes and their response to therapy has only partially been explained by genetic and transcriptomic profiling. Here, we perform comprehensive multi-omic analyses of 49 readily available childhood ALL cell lines, using proteomics, transcriptomics, and pharmacoproteomic characterization. We connect the molecular phenotypes with drug responses to 528 oncology drugs, identifying drug correlations as well as lineage-dependent correlations. We also identify the diacylglycerol-analog bryostatin-1 as a therapeutic candidate in the MEF2D-HNRNPUL1 fusion high-risk subtype, for which this drug activates pro-apoptotic ERK signaling associated with molecular mediators of pre-B cell negative selection. Our data is the foundation for the interactive online Functional Omics Resource of ALL (FORALL) with navigable proteomics, transcriptomics, and drug sensitivity profiles at https://proteomics.se/forall .
(© 2022. The Author(s).)
Databáze: MEDLINE
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