A human genome editing–based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features

Author:

Bueno Clara123ORCID,Torres-Ruiz Raul14567ORCID,Velasco-Hernandez Talia12ORCID,Molina Oscar12ORCID,Petazzi Paolo1,Martinez Alba12,Rodriguez Virginia12,Vinyoles Meritxell12ORCID,Cantilena Sandra8ORCID,Williams Owen8,Vega-Garcia Nerea910ORCID,Rodriguez-Perales Sandra7ORCID,Segovia Jose C.456ORCID,Quintana-Bustamante Oscar456ORCID,Roy Anindita1112,Meyer Claus13,Marschalek Rolf13ORCID,Smith Alastair L.11ORCID,Milne Thomas A.11ORCID,Fraga Mario F.61415ORCID,Tejedor Juan Ramón61415ORCID,Menéndez Pablo1231617ORCID

Affiliation:

1. 1Stem Cell Biology, Immunotherapy and Developmental Leukemia Laboratory. Josep Carreras Leukemia Research Institute, Barcelona, Spain

2. 2Spanish Network for Advanced Therapies, Carlos III Health Institute, Barcelona, Spain

3. 3Spanish Collaborative Cancer Network, Carlos III Health Institute, Barcelona, Spain

4. 4Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain

5. 5Advanced Therapies Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain

6. 6Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain

7. 7Molecular Cytogenetics and Genome Editing Unit, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain

8. 8Development Biology Cancer Program, Cancer Section, UCLGOS Institute of Child Health, London, United Kingdom

9. 9Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain

10. 10Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain

11. 11MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford Biomedical Research Center Hematology Theme, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom

12. 12Department of Pediatrics and National Institute for Health and Care Research Oxford Biomedical Research Centre Hematology Theme, University of Oxford, Oxford, United Kingdom

13. 13Diagnostic Center of Acute Leukemia–Institute of Pharmaceutical Biology, Goethe-University, Frankfurt/Main, Germany

14. 14Cancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center, El Entrego, Spain

15. 15Health Research Institute of Asturias, Institute of Oncology of Asturias and Department of Organisms and Systems Biology, University of Oviedo, Oviedo, Spain

16. 16Department of Biomedicine, University of Barcelona, Barcelona, Spain

17. 17Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

Abstract

Abstract Cellular ontogeny and MLL breakpoint site influence the capacity of MLL-edited CD34+ hematopoietic cells to initiate and recapitulate infant patients' features in pro–B-cell acute lymphoblastic leukemia (B-ALL). We provide key insights into the leukemogenic determinants of MLL-AF4+ infant B-ALL.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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