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

Isabelle Rose Leo, Luay Aswad, Matthias Stahl, Elena Kunold, Frederik Post, Tom Erkers, Nona Struyf, Georgios Mermelekas, Rubin Narayan Joshi, Eva Gracia-Villacampa, Päivi Östling, Olli P. Kallioniemi, Katja Pokrovskaja Tamm, Ioannis Siavelis, Janne Lehtiö, Mattias Vesterlund and Rozbeh Jafari ()
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Isabelle Rose Leo: Karolinska Institutet, Science for Life Laboratory
Luay Aswad: Karolinska Institutet, Science for Life Laboratory
Matthias Stahl: Karolinska Institutet, Science for Life Laboratory
Elena Kunold: Karolinska Institutet, Science for Life Laboratory
Frederik Post: Karolinska Institutet, Science for Life Laboratory
Tom Erkers: Karolinska Institutet, Science for Life Laboratory
Nona Struyf: Karolinska Institutet, Science for Life Laboratory
Georgios Mermelekas: Karolinska Institutet, Science for Life Laboratory
Rubin Narayan Joshi: Karolinska Institutet, Science for Life Laboratory
Eva Gracia-Villacampa: Biotechnology and Health, KTH, Science for Life Laboratory
Päivi Östling: Karolinska Institutet, Science for Life Laboratory
Olli P. Kallioniemi: Karolinska Institutet, Science for Life Laboratory
Katja Pokrovskaja Tamm: Karolinska Institutet, J6:140 BioClinicum
Ioannis Siavelis: Karolinska Institutet, Science for Life Laboratory
Janne Lehtiö: Karolinska Institutet, Science for Life Laboratory
Mattias Vesterlund: Karolinska Institutet, Science for Life Laboratory
Rozbeh Jafari: Karolinska Institutet, Science for Life Laboratory

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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 .

Date: 2022
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DOI: 10.1038/s41467-022-29224-5

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