dc.creator | Tsiftsoglou, A. S. | en |
dc.creator | Pappas, I. S. | en |
dc.creator | Vizirianakis, I. S. | en |
dc.date.accessioned | 2015-11-23T10:51:26Z | |
dc.date.available | 2015-11-23T10:51:26Z | |
dc.date.issued | 2003 | |
dc.identifier | 10.1016/j.pharmthera.2003.09.002 | |
dc.identifier.issn | 1637258 | |
dc.identifier.uri | http://hdl.handle.net/11615/33900 | |
dc.description.abstract | Despite the remarkable progress achieved in the treatment of leukemias over the last several years, many problems (multidrug resistance [MDR], cellular heterogeneity, heterogeneous molecular abnormalities, karyotypic instability, and lack of selective action of antineoplastic agents) still remain. The recent progress in tumor molecular biology has revealed that leukemias are likely to arise from disruption of differentiation of early hematopoietic progenitors that fail to give birth to cell lineage restricted phenotypes. Evidence supporting such mechanisms has been derived from studying bone marrow leukemiogenesis and analyzing differentiation of leukemic cell lines in culture that serve as models of erythroleukemic (murine erythroleukemia [MEL] and human leukemia [K562] cells) and myeloid (human promyelocytic leukemia [HL-60] cells) cell maturation. This paper reviews the current concepts of differentiation, the chemical/pharmacological inducing agents developed thus far, and the mechanisms involved in initiation of leukemic cell differentiation. Emphasis was given on commitment and the cell lineage transcriptional factors as key regulators of terminal differentiation as well as on membrane-mediated events and signaling pathways involved in hematopoietic cell differentiation. The developmental program of MEL cells was presented in considerable depth. It is quite remarkable that the erythrocytic maturation of these cells is orchestrated into specific subprograms and gene expression patterns, suggesting that leukemic cell differentiation represents a highly coordinated set of events that lead to irreversible growth arrest and expression of cell lineage restricted phenotypes. In MEL and other leukemic cells, differentiation appears to be accompanied by differentiation-dependent apoptosis (DDA), an event that can be exploited chemotherapeutically. The mechanisms by which the chemical inducers promote differentiation of leukemic cells have been discussed. © 2003 Elsevier Inc. All rights reserved. | en |
dc.source.uri | http://www.scopus.com/inward/record.url?eid=2-s2.0-0344255770&partnerID=40&md5=b1475c7566159d0aeb30bbee3a08dbd8 | |
dc.subject | Apoptosis | en |
dc.subject | Chemical inducers | en |
dc.subject | Differentiation | en |
dc.subject | Hematopoietic cells | en |
dc.subject | Leukemia | en |
dc.subject | Mechanisms | en |
dc.subject | 2 pyridone derivative | en |
dc.subject | 20 epi 22 ethoxy 24a,26a,27a trihomo 9,10 secocholesta 5,7,10(19) trien 23 yne 1alpha,3beta,25 triol | en |
dc.subject | 5 aza 2' deoxycytidine | en |
dc.subject | 9,10 secocholesta 5,7,10(19),16 tetraen 23 yne 1,3,25 triol | en |
dc.subject | activin A | en |
dc.subject | amide | en |
dc.subject | antineoplastic agent | en |
dc.subject | azacitidine | en |
dc.subject | benzodiazepine | en |
dc.subject | camptothecin | en |
dc.subject | colecalciferol derivative | en |
dc.subject | cytokine | en |
dc.subject | dactinomycin | en |
dc.subject | dimethyl sulfoxide | en |
dc.subject | DNA topoisomerase inhibitor | en |
dc.subject | flucytosine deoxyriboside | en |
dc.subject | fluorouracil | en |
dc.subject | hemin | en |
dc.subject | hexamethylenebisacetamide | en |
dc.subject | histone deacetylase inhibitor | en |
dc.subject | imatinib | en |
dc.subject | inosinate dehydrogenase inhibitor | en |
dc.subject | lactam derivative | en |
dc.subject | n (2 aminophenyl) 4 (3 pyridinylmethoxycarbonylaminomethyl)benzamide | en |
dc.subject | purine derivative | en |
dc.subject | pyridine derivative | en |
dc.subject | pyrimidine derivative | en |
dc.subject | retinoid | en |
dc.subject | ro 24 5531 | en |
dc.subject | seocalcitol | en |
dc.subject | thiourea derivative | en |
dc.subject | trichostatin A | en |
dc.subject | tunicamycin | en |
dc.subject | unclassified drug | en |
dc.subject | unindexed drug | en |
dc.subject | urea derivative | en |
dc.subject | uridine diphosphate | en |
dc.subject | zebularine | en |
dc.subject | acetylation | en |
dc.subject | cancer chemotherapy | en |
dc.subject | cell culture | en |
dc.subject | cell cycle | en |
dc.subject | cell differentiation | en |
dc.subject | cell growth | en |
dc.subject | cell maturation | en |
dc.subject | cell membrane | en |
dc.subject | cell proliferation | en |
dc.subject | cell survival | en |
dc.subject | chromatin | en |
dc.subject | chromatin condensation | en |
dc.subject | DNA methylation | en |
dc.subject | DNA replication | en |
dc.subject | drug effect | en |
dc.subject | drug potency | en |
dc.subject | erythroleukemia cell | en |
dc.subject | Friend leukemia | en |
dc.subject | gene activation | en |
dc.subject | gene expression | en |
dc.subject | gene repression | en |
dc.subject | genetic transfection | en |
dc.subject | hematopoiesis | en |
dc.subject | hematopoietic cell | en |
dc.subject | hematopoietic stem cell | en |
dc.subject | human | en |
dc.subject | leukemia cell | en |
dc.subject | mesenchyme cell | en |
dc.subject | mitosis inhibition | en |
dc.subject | molecular cloning | en |
dc.subject | nonhuman | en |
dc.subject | Northern blotting | en |
dc.subject | oncogene c myc | en |
dc.subject | phenotype | en |
dc.subject | priority journal | en |
dc.subject | promoter region | en |
dc.subject | promyelocytic leukemia | en |
dc.subject | protein expression | en |
dc.subject | protein interaction | en |
dc.subject | protein phosphorylation | en |
dc.subject | proto oncogene | en |
dc.subject | receptor binding | en |
dc.subject | review | en |
dc.subject | RNA methylation | en |
dc.subject | signal transduction | en |
dc.subject | stem cell | en |
dc.subject | Animals | en |
dc.subject | Antineoplastic Agents | en |
dc.subject | Gene Expression Regulation, Neoplastic | en |
dc.subject | Humans | en |
dc.subject | Leukemia, Experimental | en |
dc.subject | Mice | en |
dc.title | Mechanisms involved in the induced differentiation of leukemia cells | en |
dc.type | journalArticle | en |