The PML-RAR alpha gene product of the t(15;17) translocation inhibits retinoic acid-induced granulocytic differentiation and mediated transactivation in human myeloid cells
| Autor: | Rousselot P, Hardas B, Patel A, Fabien Guidez, Gäken J, Castaigne S, Dejean A, de Thé H, Degos L, Farzaneh F |
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| Rok vydání: | 1994 |
| Předmět: |
Transcriptional Activation
Receptors Retinoic Acid Recombinant Fusion Proteins Molecular Sequence Data Bone Marrow Cells Tretinoin Promyelocytic Leukemia Protein Transfection Translocation Genetic Cell Line Leukemia Promyelocytic Acute Bone Marrow Tumor Cells Cultured Humans Cholecalciferol Chromosomes Human Pair 15 Base Sequence Dose-Response Relationship Drug Retinoic Acid Receptor alpha Tumor Suppressor Proteins Nuclear Proteins Cell Differentiation DNA Neoplasm Neoplasm Proteins Chromosomes Human Pair 17 Granulocytes Transcription Factors |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0950-9232 |
| Popis: | Acute promyelocytic leukemia (APL) is characterized by an arrest of granulocytic differentiation and a reciprocal t(15;17) translocation fusing the PML gene to the retinoic acid receptor alpha (RAR alpha) gene. PML was recently identified as a potential transcription factor. In non hematopoietic cells, the transfected PML-RAR alpha product binds all trans retinoic acid and exhibits altered transactivating properties when compared with RAR alpha. A major question raised by these observations is whether PML-RAR alpha contributes to the inhibition of myeloid differentiation. We find that in myeloid cell lines responsive to retinoic acid, PML-RAR alpha blocks retinoic acid mediated transactivation and totally abrogates the retinoic acid mediated granulocytic differentiation. These findings strongly suggest that PML-RAR alpha may, by blocking normal retinoic acid dependent myeloid differentiation, participate in the leukemogenesis of APL. The fact that high doses of all-trans retinoic acid relieve the inhibitory effect of PML-RAR alpha corroborates the therapeutic effect of all-trans retinoic acid in APL patients. |
| Databáze: | OpenAIRE |
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