Integrative methylome-transcriptome analysis unravels cancer-cell vulnerabilities in infant MLL-rearranged B-ALL (Datasets and additional tables))

  1. Tejedor, Juan Ramón 1
  2. Bueno, Clara 2
  3. Vinyoles, Meritxell 2
  4. Petazzi, Paolo 2
  5. Agraz-Doblas, Antonio 3
  6. Cobo, Isabel 4
  7. Torres-Ruiz, Raúl 5
  8. Bayón, Gustavo F 6
  9. Pérez, Raúl F 1
  10. López-Tamargo, Sara 6
  11. Gutierrez-Agüera, Francisco 2
  12. Santamarina-Ojeda, Pablo 6
  13. Ramírez-Orellana, Manuel 7
  14. Bardini, Michela 8
  15. Cazzaniga, Gianni 8
  16. Ballerini, Paola 9
  17. Schneider, Pauline 10
  18. Stam, Ronald W 10
  19. Varela, Ignacio 11
  20. Fraga, Mario F 1
  21. Fernández, Agustín F 12
  22. Menéndez, Pablo 13
  1. 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. 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. 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. 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. 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. 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. 7 Hematology Diagnostic Laboratory. Hospital Universitario Niño Jesús, Madrid. Spain
  8. 8 Centro Ricerca Tettamanti, Department of Paediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy
  9. 9 Pediatric Hematology. Armand Trousseau Hospital. Paris. France
  10. 10 Princess Maxima Center for Paediatric Oncology, Utrecht, The Netherlands
  11. 11 Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC, Santander, Spain
  12. 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. 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
Zugehörigkeit anzeigen +

Verleger: Zenodo

Datum der Publikation: 2021

Art: Dataset

CC BY 4.0

DOI: 10.5281/ZENODO.3695640 lock_openOpen Access editor

Zusammenfassung

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 <em>de novo</em> 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 <em>in vitro</em> and <em>in vivo</em> 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.