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

Bueno, Clara; Torres-Ruiz, Raul; Velasco-Hernandez, Talia; Molina, Oscar; Petazzi, Paolo; Martinez, Alba; Rodriguez, Virginia; Vinyoles, Meritxell; Cantilena, Sandra; Williams, Owen; Vega-Garcia, Nerea; Rodriguez-Perales, Sandra; Segovia, Jose C.; Quintana-Bustamante, Oscar; Roy, Anindita; Meyer, Claus; Marschalek, Rolf; Smith, Alastair L.; Milne, Thomas A.; Fraga, Mario F.; Tejedor, Juan Ramón; Menéndez, Pablo

doi:10.1182/blood.2023020858

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Letter to Blood| November 16, 2023

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

Clara Bueno,

Clara Bueno

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

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

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

https://orcid.org/0000-0003-1442-6216

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Raul Torres-Ruiz,

Raul Torres-Ruiz

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

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

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

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

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

https://orcid.org/0000-0001-9606-0398

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Talia Velasco-Hernandez,

Talia Velasco-Hernandez

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

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

https://orcid.org/0000-0003-2183-7443

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Oscar Molina,

Oscar Molina

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

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

https://orcid.org/0000-0001-7585-4519

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Paolo Petazzi,

Paolo Petazzi

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

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Alba Martinez,

Alba Martinez

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

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

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Virginia Rodriguez,

Virginia Rodriguez

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

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

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Meritxell Vinyoles,

Meritxell Vinyoles

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

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

https://orcid.org/0000-0003-1906-4701

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Sandra Cantilena,

Sandra Cantilena

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

https://orcid.org/0000-0002-1986-7873

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Owen Williams,

Owen Williams

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

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Nerea Vega-Garcia,

Nerea Vega-Garcia

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

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

https://orcid.org/0000-0002-3190-063X

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Sandra Rodriguez-Perales,

Sandra Rodriguez-Perales

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

https://orcid.org/0000-0001-7221-3636

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Jose C. Segovia,

Jose C. Segovia

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

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

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

https://orcid.org/0000-0003-4101-6124

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Oscar Quintana-Bustamante,

Oscar Quintana-Bustamante

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

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

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

https://orcid.org/0000-0002-6869-7006

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Anindita Roy,

Anindita Roy

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

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

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Claus Meyer,

Claus Meyer

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

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Rolf Marschalek,

Rolf Marschalek

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

https://orcid.org/0000-0003-4870-3445

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Alastair L. Smith,

Alastair L. Smith

https://orcid.org/0000-0001-6330-1407

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Thomas A. Milne,

Thomas A. Milne

https://orcid.org/0000-0002-0413-4271

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Mario F. Fraga,

Mario F. Fraga

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

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

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

https://orcid.org/0000-0001-8450-2603

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Juan Ramón Tejedor,

Juan Ramón Tejedor

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

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

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

https://orcid.org/0000-0002-4061-9698

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Pablo Menéndez

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

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

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

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

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

https://orcid.org/0000-0001-9372-1007

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Blood (2023) 142 (20): 1752–1756.

https://doi.org/10.1182/blood.2023020858

Article history

Submitted:

April 18, 2023

Accepted:

August 18, 2023

First Edition:

September 26, 2023

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Citation

Clara Bueno, Raul Torres-Ruiz, Talia Velasco-Hernandez, Oscar Molina, Paolo Petazzi, Alba Martinez, Virginia Rodriguez, Meritxell Vinyoles, Sandra Cantilena, Owen Williams, Nerea Vega-Garcia, Sandra Rodriguez-Perales, Jose C. Segovia, Oscar Quintana-Bustamante, Anindita Roy, Claus Meyer, Rolf Marschalek, Alastair L. Smith, Thomas A. Milne, Mario F. Fraga, Juan Ramón Tejedor, Pablo Menéndez; A human genome editing–based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features. Blood 2023; 142 (20): 1752–1756. doi: https://doi.org/10.1182/blood.2023020858

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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.

Subjects:

Lymphoid Neoplasia

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

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