MYC as therapeutic target in leukemia and lymphoma

Maria G Cortiguera,1 Ana Batlle-López,1,2 Marta Albajar,1,2 M Dolores Delgado,1,3 Javier León1,3 1Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, 2Department of Hemathology, Hospital Universitario Marqués de Valdecilla,...

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Autores principales:	Cortiguera MG, Batlle-López A, Albajar M, Delgado MD, León J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/14e4c91029424c2982ade83ed28c1bfe
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spelling	oai:doaj.org-article:14e4c91029424c2982ade83ed28c1bfe2021-12-02T03:00:57ZMYC as therapeutic target in leukemia and lymphoma1179-9889https://doaj.org/article/14e4c91029424c2982ade83ed28c1bfe2015-07-01T00:00:00Zhttp://www.dovepress.com/myc-as-therapeutic-target-in-leukemia-and-lymphoma-peer-reviewed-article-BLCTThttps://doaj.org/toc/1179-9889Maria G Cortiguera,1 Ana Batlle-López,1,2 Marta Albajar,1,2 M Dolores Delgado,1,3 Javier León1,3 1Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, 2Department of Hemathology, Hospital Universitario Marqués de Valdecilla, 3Department of Molecular Biology, University of Cantabria, Santander, Spain Abstract: MYC is a transcription factor that is involved in the expression of many genes. Deregulated MYC is found in about half of human tumors, being more prevalent in hematological neoplasms. Deregulation mechanisms include chromosomal translocation (particularly in lymphoma), amplification, and hyperactivation of MYC transcription. Here we review MYC involvement in the major types of leukemia and lymphoma. MYC rearrangements appear in all Burkitt lymphomas and are common in other lymphoma types, whereas in acute lymphoblastic leukemia, acute myeloid leukemia, lymphoproliferative, and myeloproferative diseases, they are less frequent. However, MYC overexpression is present in all types of hematological malignancies and often correlates with a worse prognosis. Data in leukemia-derived cells and in animal models of lymphomagenesis and leukemogenesis suggest that MYC would be a good therapeutic target. Several MYC-directed therapies have been assayed in preclinical settings and even in clinical trials. First, peptides and small molecules that interrupt the MYC–MAX interaction impair MYC-mediated tumorogenesis in several mouse models of solid tumors, although not yet in lymphoma and leukemia models. Second, there are a number of small molecules inhibiting the interaction of MYC–MAX heterodimers with DNA, still in the preclinical research phase. Third, inhibitors of MYC expression via the inhibition of BRD4 (a reader of acetylated histones) have been shown to control the growth of MYC-transformed leukemia and lymphoma cells and are being used in clinic trials. Finally, we review a number of promising MYC-mediated synthetic lethal approaches that are under study and have been tested in hematopoietic neoplasms. Keywords: MYC, targeted therapy, leukemia, lymphoma Cortiguera MGBatlle-López AAlbajar MDelgado MDLeón JDove Medical PressarticleDiseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol 2015, Iss default, Pp 75-91 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	Diseases of the blood and blood-forming organs RC633-647.5 Cortiguera MG Batlle-López A Albajar M Delgado MD León J MYC as therapeutic target in leukemia and lymphoma
description	Maria G Cortiguera,1 Ana Batlle-López,1,2 Marta Albajar,1,2 M Dolores Delgado,1,3 Javier León1,3 1Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, 2Department of Hemathology, Hospital Universitario Marqués de Valdecilla, 3Department of Molecular Biology, University of Cantabria, Santander, Spain Abstract: MYC is a transcription factor that is involved in the expression of many genes. Deregulated MYC is found in about half of human tumors, being more prevalent in hematological neoplasms. Deregulation mechanisms include chromosomal translocation (particularly in lymphoma), amplification, and hyperactivation of MYC transcription. Here we review MYC involvement in the major types of leukemia and lymphoma. MYC rearrangements appear in all Burkitt lymphomas and are common in other lymphoma types, whereas in acute lymphoblastic leukemia, acute myeloid leukemia, lymphoproliferative, and myeloproferative diseases, they are less frequent. However, MYC overexpression is present in all types of hematological malignancies and often correlates with a worse prognosis. Data in leukemia-derived cells and in animal models of lymphomagenesis and leukemogenesis suggest that MYC would be a good therapeutic target. Several MYC-directed therapies have been assayed in preclinical settings and even in clinical trials. First, peptides and small molecules that interrupt the MYC–MAX interaction impair MYC-mediated tumorogenesis in several mouse models of solid tumors, although not yet in lymphoma and leukemia models. Second, there are a number of small molecules inhibiting the interaction of MYC–MAX heterodimers with DNA, still in the preclinical research phase. Third, inhibitors of MYC expression via the inhibition of BRD4 (a reader of acetylated histones) have been shown to control the growth of MYC-transformed leukemia and lymphoma cells and are being used in clinic trials. Finally, we review a number of promising MYC-mediated synthetic lethal approaches that are under study and have been tested in hematopoietic neoplasms. Keywords: MYC, targeted therapy, leukemia, lymphoma
format	article
author	Cortiguera MG Batlle-López A Albajar M Delgado MD León J
author_facet	Cortiguera MG Batlle-López A Albajar M Delgado MD León J
author_sort	Cortiguera MG
title	MYC as therapeutic target in leukemia and lymphoma
title_short	MYC as therapeutic target in leukemia and lymphoma
title_full	MYC as therapeutic target in leukemia and lymphoma
title_fullStr	MYC as therapeutic target in leukemia and lymphoma
title_full_unstemmed	MYC as therapeutic target in leukemia and lymphoma
title_sort	myc as therapeutic target in leukemia and lymphoma
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/14e4c91029424c2982ade83ed28c1bfe
work_keys_str_mv	AT cortigueramg mycastherapeutictargetinleukemiaandlymphoma AT batllelopeza mycastherapeutictargetinleukemiaandlymphoma AT albajarm mycastherapeutictargetinleukemiaandlymphoma AT delgadomd mycastherapeutictargetinleukemiaandlymphoma AT leonj mycastherapeutictargetinleukemiaandlymphoma
_version_	1718401964811747328

MYC as therapeutic target in leukemia and lymphoma

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