Epigenetic-based differentiation therapy for Acute Myeloid Leukemia.

Humans Cell Differentiation / drug effects Leukemia, Myeloid, Acute / genetics Epigenesis, Genetic / drug effects Histone Deacetylase Inhibitors / pharmacology Cell Line, Tumor Acetylation / drug effects Transcription Factors / metabolism Gene Expression Regulation, Leukemic / drug effects Animals

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 Jul 2024
Historique:
received: 02 02 2023
accepted: 18 06 2024
medline: 3 7 2024
pubmed: 3 7 2024
entrez: 2 7 2024
Statut: epublish

Résumé

Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer-promoter chromatin regulatory complex, including bromodomain proteins. This acetylation is essential for enhancing the expression of key transcription factors directly involved in the differentiation therapy induced by CM-444/CM-1758 in acute myeloid leukemia. In summary, these compounds may represent effective differentiation-based therapeutic agents across acute myeloid leukemia subtypes with a potential mechanism for the treatment of acute myeloid leukemia.

Identifiants

DOI: 10.1038/s41467-024-49784-y PMID: 38956053
pubmed: 38956053
doi: 10.1038/s41467-024-49784-y
pii: 10.1038/s41467-024-49784-y
doi:

Substances chimiques

Histone Deacetylase Inhibitors 0
Transcription Factors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5570

Subventions

Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : PI19/01352, PI22/00947
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : PI20/01306, PI23/00488
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : CB16/12/00369
Organisme : Departamento de Educación, Gobierno de Navarra (Department of Education, Government of Navarra)
ID : 44/2021; 0011-1411-2022-000068
Organisme : Departamento de Educación, Gobierno de Navarra (Department of Education, Government of Navarra)
ID : GN2023/11
Organisme : International Myeloma Foundation (IMF)
ID : Brian van Novis
Organisme : "la Caixa" Foundation (Caixa Foundation)
ID : GR-NET NORMAL-HIT HR20-00871

Informations de copyright

© 2024. The Author(s).

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Auteurs

Edurne San José-Enériz (E)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.
ORCID: 0000-0001-5786-5273

Naroa Gimenez-Camino (N)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.

Obdulia Rabal (O)

Small-Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Avenida Pío XII 55, 31008, Pamplona, Spain.

Leire Garate (L)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.

Estibaliz Miranda (E)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.

Nahia Gómez-Echarte (N)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
ORCID: 0000-0002-9924-0965

Fernando García (F)

ProteoRed-ISCIII, Unidad de Proteómica, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain.
ORCID: 0000-0003-3888-4326

Stella Charalampopoulou (S)

Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Casanova 143, 08036, Barcelona, Spain.

Elena Sáez (E)

Small-Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Avenida Pío XII 55, 31008, Pamplona, Spain.

Amaia Vilas-Zornoza (A)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.

Patxi San Martín-Uriz (P)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
ORCID: 0000-0003-1483-4279

Luis V Valcárcel (LV)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.
TECNUN, Universidad de Navarra, Manuel de Lardizábal 13, 20018, San Sebastián, Spain.
ORCID: 0000-0003-3769-5419

Naroa Barrena (N)

TECNUN, Universidad de Navarra, Manuel de Lardizábal 13, 20018, San Sebastián, Spain.
ORCID: 0000-0003-4324-3371

Diego Alignani (D)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.

Luis Esteban Tamariz-Amador (LE)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.
Departmento de Hematología, Clínica Universidad de Navarra, and CCUN, Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
ORCID: 0000-0002-4088-0992

Ana Pérez-Ruiz (A)

Biomedical Engineering Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, Avenida Pío XII 55, 31008, Pamplona, Spain.
ORCID: 0000-0002-9901-057X

Sebastian Hilscher (S)

Department of Enzymology, Charles Tanford Protein Center, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, 06120, Halle, Germany.
Department of Medicinal Chemistry, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, 06120, Halle, Germany.
ORCID: 0009-0003-0611-7365

Mike Schutkowski (M)

Department of Enzymology, Charles Tanford Protein Center, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, 06120, Halle, Germany.
Department of Medicinal Chemistry, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, 06120, Halle, Germany.

Ana Alfonso-Pierola (A)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.
Departmento de Hematología, Clínica Universidad de Navarra, and CCUN, Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
ORCID: 0000-0002-2478-5354

Nicolás Martinez-Calle (N)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.
Departmento de Hematología, Clínica Universidad de Navarra, and CCUN, Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.

María José Larrayoz (MJ)

CIMA LAB Diagnostics, Universidad de Navarra, Avenida Pío XII 55, 31008, Pamplona, Spain.
ORCID: 0000-0003-0667-1959

Bruno Paiva (B)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.
ORCID: 0000-0003-1977-3815

María José Calasanz (MJ)

CIMA LAB Diagnostics, Universidad de Navarra, Avenida Pío XII 55, 31008, Pamplona, Spain.
ORCID: 0000-0002-0374-3008

Javier Muñoz (J)

Biocruces Bizkaia Health Research Institute, Cruces Plaza, 48903, Barakaldo, Spain.
Ikerbasque, Basque Foundation for Science, Plaza Euskadi 5, 48009, Bilbao, Spain.
ORCID: 0000-0003-3288-3496

Marta Isasa (M)

ProteoRed-ISCIII, Unidad de Proteómica, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain.

José Ignacio Martin-Subero (JI)

Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain.
Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Casanova 143, 08036, Barcelona, Spain.
Departamento de Fundamentos Clínicos, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig de Lluís Companys 23, 08010, Barcelona, Spain.
ORCID: 0000-0001-8809-5195

Antonio Pineda-Lucena (A)

Small-Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Avenida Pío XII 55, 31008, Pamplona, Spain.

Julen Oyarzabal (J)

Small-Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Avenida Pío XII 55, 31008, Pamplona, Spain. julenoyarzabal@external.unav.es.

Xabier Agirre (X)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain. xaguirre@unav.es.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain. xaguirre@unav.es.
ORCID: 0000-0002-6558-9560

Felipe Prósper (F)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, IDISNA, CCUN, Avenida Pío XII 55, 31008, Pamplona, Spain. fprosper@unav.es.
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain. fprosper@unav.es.
Departmento de Hematología, Clínica Universidad de Navarra, and CCUN, Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain. fprosper@unav.es.
ORCID: 0000-0001-6115-8790

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Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

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