Targeting aberrant transcriptional repression in acute myeloid leukemia Journal Article
| Authors: | Moe-Behrens, G. H. G.; Pandolfi, P. P. |
| Article Title: | Targeting aberrant transcriptional repression in acute myeloid leukemia |
| Abstract: | Histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities determine the acetylation status of histones, and have the ability to regulate gene expression through chromatin remodeling. Aberrant histone acetylation is known to play a key role in leukemogenesis. A common biologic feature, shared by genetically heterogeneous acute myeloid leukemias (AML), is a block of hematopoietic differentiation by the fusion proteins produced by chromosomal translocations. In many cases, a DNA binding fusion protein, which abnormally interacts with transcriptional co-regulators and increases local concentration of HDAC complexes, imposes a transcriptional repressive state on target gene promoters, which may become refractory to physiologic stimuli. To target this transcriptional repression, HDAC inhibitors (HDACI) have been developed, which are thought to derepress a set of genes whose transcriptional activation induces cell-cycle arrest, apoptosis and cellular differentiation and thus anti-tumoral activity. Therefore, HDACI might be utilized as effective antileukemic agents, and are currently under clinical trials. |
| Keywords: | cancer chemotherapy; treatment outcome; unclassified drug; acute granulocytic leukemia; promoter region; histone deacetylase inhibitor; clinical trial; drug activity; fatigue; neutropenia; pathogenesis; review; cancer recurrence; cancer combination chemotherapy; dose response; side effect; antineoplastic agent; cell cycle; gene overexpression; apoptosis; enzyme inhibition; gene expression; transcription initiation; nausea; thrombocytopenia; protein interaction; cell differentiation; transcription, genetic; antineoplastic activity; drug effect; enzyme activity; dna methylation; acute lymphoblastic leukemia; carcinogenesis; chemotherapy induced emesis; gene expression regulation, neoplastic; cancer regression; t cell lymphoma; myelodysplastic syndrome; hybrid protein; drug mechanism; enzyme inhibitors; chromatin; cardiotoxicity; leukemogenesis; leukemia, myeloid; acute myeloblastic leukemia; promyelocytic leukemia; beta thalassemia; vorinostat; chromosome translocation; 5 aza 2' deoxycytidine; dna binding; chronic lymphatic leukemia; chromosome 11; histone deacetylases; retinoic acid; ligand binding; hydroxamic acid; chromosome 17; azacitidine; multidrug resistance; acetyltransferases; valproic acid; histone deacetylase; acute disease; n (2 aminophenyl) 4 (3 pyridinylmethoxycarbonylaminomethyl)benzamide; trapoxin; trichostatin a; acetylation; ecg abnormality; chromatin structure; depsipeptide; retinoic acid receptor alpha; benzamide derivative; nicotinamide; teratogenicity; chromosome 5; histone acetyltransferase; histone acetyltransferases; fr 901228; retinoid x receptor; oxamflatin; butyric acid derivative; apicidin; tetrapeptide; humans; human; 3 carboxycinnamic acid bishydroxic acid; cl 994; depudecin; proxamide; sodium phenylbutyrate; splitomycin |
| Journal Title: | Reviews in Clinical and Experimental Hematology |
| Volume: | 7 |
| Issue: | 2 |
| ISSN: | 1127-0020 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2003-06-01 |
| Start Page: | 139 |
| End Page: | 159 |
| Language: | English |
| PUBMED: | 14763160 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 25 September 2014 -- Source: Scopus |
