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Integrative multi-o...
Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines
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- Leo, Isabelle Rose (author)
- Karolinska Institutet
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- Aswad, Luay (author)
- Karolinska Institutet
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- Stahl, Matthias (author)
- Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Sci Life Lab, Tomtebodavagen 23A, S-17165 Solna, Sweden.
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- Kunold, Elena (author)
- Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Sci Life Lab, Tomtebodavagen 23A, S-17165 Solna, Sweden.
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- Post, Frederik (author)
- Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Sci Life Lab, Tomtebodavagen 23A, S-17165 Solna, Sweden.;Univ Munster, Inst Plant Biol & Biotechnol, Schlosspl 7, D-48149 Munster, Germany.
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- Erkers, Tom (author)
- Karolinska Institutet
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- Struyf, Nona (author)
- Karolinska Institutet
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- Mermelekas, Georgios (author)
- Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Sci Life Lab, Tomtebodavagen 23A, S-17165 Solna, Sweden.
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- Joshi, Rubin Narayan (author)
- Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Sci Life Lab, Tomtebodavagen 23A, S-17165 Solna, Sweden.
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- Villacampa, Eva Gracia (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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- Ostling, Paivi (author)
- Karolinska Institutet
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- Kallioniemi, Olli P. (author)
- Karolinska Inst, Sci Life Lab, Dept Oncol Pathol, Mol Precis Med, Tomtebodavagen 23A, S-17165 Solna, Sweden.
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- Tamm, Katja Pokrovskaja (author)
- Karolinska Institutet
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- Siavelis, Ioannis (author)
- Karolinska Institutet
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- Lehtio, Janne (author)
- Karolinska Institutet
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- Vesterlund, Mattias (author)
- Karolinska Institutet
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- Jafari, Rozbeh (author)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Sci Life Lab, Tomtebodavagen 23A, S-17165 Solna, Sweden (creator_code:org_t)
- 2022-03-30
- 2022
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- 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/fora.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Leo, Isabelle Ro ...
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Aswad, Luay
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Stahl, Matthias
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Kunold, Elena
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Post, Frederik
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Erkers, Tom
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Struyf, Nona
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Mermelekas, Geor ...
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Joshi, Rubin Nar ...
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Villacampa, Eva ...
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Ostling, Paivi
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Kallioniemi, Oll ...
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Tamm, Katja Pokr ...
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Siavelis, Ioanni ...
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Lehtio, Janne
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Vesterlund, Matt ...
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Jafari, Rozbeh
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Nature Communica ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet