title: The transcriptional repressor HDAC7 promotes apoptosis and c-Myc downregulation in particular types of leukemia and lymphoma.
abstract: The generation of B cells is a complex process requiring several cellular transitions, including cell commitment and differentiation. Proper transcriptional control to establish the genetic programs characteristic of each cellular stage is essential for the correct development of B lymphocytes. Deregulation of these particular transcriptional programs may result in a block in B-cell maturation, contributing to the development of hematological malignancies such as leukemia and lymphoma. However, very little is currently known about the role of transcriptional repressors in normal and aberrant B lymphopoiesis. Here we report that histone deacetylase 7 (HDAC7) is underexpressed in pro-B acute lymphoblastic leukemia (pro-B-ALL) and Burkitt lymphoma. Ectopic expression of HDAC7 induces apoptosis, leads to the downregulation of c-Myc and inhibits the oncogenic potential of cells in vivo, in a xenograft model. Most significantly, we have observed low levels of HDAC7 expression in B-ALL patient samples, which is correlated with the increased levels of c-Myc. From a mechanistic angle, we show that ectopically expressed HDAC7 localizes to the nucleus and interacts with the transcription factor myocyte enhancer factor C (MEF2C) and the corepressors HDAC3 and SMRT. Accordingly, both the HDAC7-MEF2C interaction domain as well as its catalytic domain are involved in the reduced cell viability induced by HDAC7. We conclude that HDAC7 has a potent anti-oncogenic effect on specific B-cell malignancies, indicating that its deregulation may contribute to the pathogenesis of the disease.
authors: Cellular Differentiation Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain.
authors: B
authors: B
authors: Barneda-Zahonero
authors: Cellular Differentiation Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain.
authors: O
authors: O
authors: Collazo
authors: Cellular Differentiation Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain.
authors: A
authors: A
authors: Azagra
authors: Cellular Differentiation Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain.
authors: I
authors: I
authors: Fernández-Duran
authors: Breast Cancer and Systems Biology Unit, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Avenida Gran Via s/n km 2.7, 08907 L'Hospitalet, Barcelona, Spain.
authors: J
authors: J
authors: Serra-Musach
authors: Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh.
authors: A B M M K
authors: AB
authors: Islam
authors: Department of Hematology, Hospital Sant Joan de Déu, Barcelona, Spain.
authors: N
authors: N
authors: Vega-García
authors: Department of Hematology, Hospital Sant Joan de Déu, Barcelona, Spain.
authors: R
authors: R
authors: Malatesta
authors: Department of Hematology, Hospital Sant Joan de Déu, Barcelona, Spain.
authors: M
authors: M
authors: Camós
authors: Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain.
authors: A
authors: A
authors: Gómez
authors: Cellular Differentiation Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain.
authors: L
authors: L
authors: Román-González
authors: Department of Pathology, University Hospital of Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors: A
authors: A
authors: Vidal
authors: 1] Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors: N
authors: N
authors: López-Bigas
authors: Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors: A
authors: A
authors: Villanueva
authors: 1] Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain [3] Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain.
authors: M
authors: M
authors: Esteller
authors: Cellular Differentiation Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research institute (IDIBELL), Avenida Gran Via 199, 08908 L'Hospitalet, Barcelona, Spain.
authors: M
authors: M
authors: Parra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D000067470:Cellular Reprogramming Techniques; D015536:Down-Regulation / Q000235:genetics*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D064326:MEF2 Transcription Factors; D056985:Nuclear Receptor Co-Repressor 2; D016271:Proto-Oncogene Proteins c-myc; D000099186:Histone Deacetylase 3