Integrative methylome-transcriptome analysis unravels cancer-cell vulnerabilities in infant MLL-rearranged B-ALL (Datasets and additional tables))
Creators
- Juan Ramón Tejedor1
- Clara Bueno2
- Meritxell Vinyoles2
- Paolo Petazzi2
- Antonio Agraz-Doblas3
- Isabel Cobo4
- Raúl Torres-Ruiz5
- Gustavo F Bayón6
- Raúl F Pérez1
- Sara López-Tamargo6
- Francisco Gutierrez-Agüera2
- Pablo Santamarina-Ojeda6
- Manuel Ramírez-Orellana7
- Michela Bardini8
- Gianni Cazzaniga8
- Paola Ballerini9
- Pauline Schneider10
- Ronald W Stam10
- Ignacio Varela11
- Mario F Fraga1
- Agustín F Fernández12
- Pablo Menéndez13
- 1. Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Principado de Asturias, Spain. Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo, Principado de Asturias, Spain
- 2. Josep Carreras Leukemia Research Institute-Campus Clinic, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), ISCIII, Barcelona, Spain
- 3. Josep Carreras Leukemia Research Institute-Campus Clinic, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain. Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain
- 4. Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología de Asturias (IUOPA), Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Asturias, Spain. Josep Carreras Leukemia Research Institute-Campus Clinic, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain
- 5. Josep Carreras Leukemia Research Institute-Campus Clinic, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), ISCIII, Barcelona, Spain. Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- 6. Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología de Asturias (IUOPA), Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Asturias, Spain
- 7. Hematology Diagnostic Laboratory. Hospital Universitario Niño Jesús, Madrid. Spain
- 8. Centro Ricerca Tettamanti, Department of Paediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy
- 9. Pediatric Hematology. Armand Trousseau Hospital. Paris. France
- 10. Princess Maxima Center for Paediatric Oncology, Utrecht, The Netherlands
- 11. Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain
- 12. Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Principado de Asturias, Spain
- 13. Josep Carreras Leukemia Research Institute-Campus Clinic, Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), ISCIII, Barcelona, Spain. Instituciò Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
Description
B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. As predicated by its prenatal origin, infant B-ALL (iB-ALL) shows an exceptionally silent DNA mutational landscape, suggesting that alternative epigenetic mechanisms may significantly contribute to its leukemogenesis. We have extensively characterized the DNA methylome and the transcriptome lansdcape of 40 patients with de novo MLL rearranged (MLLr) and non-MLLr iB-ALL leukemias uniformly treated according to Interfant-99/06 protocol. iB-ALL methylome signatures display a plethora of common and specific alterations associated with chromatin states related to enhancer and transcriptional control. Further methylome-transcriptome integration identified consistent cancer-cell vulnerabilities, revealed a robust iB-ALL-specific gene expression-correlating dmCpG signature and confirmed an epigenetic control of AP-1 and RUNX members in reshaping the molecular network of MLLr iB-ALL. Pharmacological inhibition or functional ablation of AP-1 activity resulted in dramatic in vitro and in vivo leukemia proliferation defects, providing rationale for new potential therapeutic avenues in iB-ALL. This dataset contains information related to dataframes, databases, scripts and supplementary material mentioned in the original manuscript.
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Additional details
Funding
- INFANTLEUKEMIA – GENOMIC, CELLULAR AND DEVELOPMENTAL RECONSTRUCTION OF INFANT MLL-AF4+ ACUTE LYMPHOBLASTIC LEUKEMIA 646903
- European Commission
- IT4B-ALL – Therapeutic immunotherapy targeting NG2 and CD22 antigens for MLL-rearranged and MLL-germline B-cell Acute Lymphoblastic Leukemia 811220
- European Commission