Acute promyelocytic leukemia as a model for cross-talk between interferon and retinoic acid pathways: From molecular biology to clinical applications Journal Article
| Authors: | Gaboli, M.; Gandini, D.; Delva, L.; Wang, Z. G.; Pandolfi, P. P. |
| Article Title: | Acute promyelocytic leukemia as a model for cross-talk between interferon and retinoic acid pathways: From molecular biology to clinical applications |
| Abstract: | Acute promyelocytic leukemia (APL) has been regarded as the paradigm for therapeutic approaches utilizing differentiating agents, due to the fact that almost 95% of patients undergo complete remission when treated with all-trans retinoic acid (ATRA). However, complete clinical remission with ATRA alone is always transient, and relapse in APL is almost invariably associated with the acquisition of resistance to ATRA. Acquired resistance to ATRA in APL cell lines and in some APL clinical cases can be partially overcome by interferons (IFNs), cytokines which have well established tumor-growth suppressive activities. APL is associated in 99% of cases with a 15;17 translocation that fuses the PML and Retinoic Acid Receptor alpha (RARα) genes. RARα is one of the Retinoic Acid (RA) nuclear receptors which mediates, at the transcriptional level, ATRA differentiating and growth suppressive activity. PML is a tumor-growth suppressor whose expression is directly regulated by IFNs. Here we review the molecular mechanisms by which IFNs and RA can cooperate in controlling cell growth and differentiation of normal hemopoietic cells and leukemic cells, focusing on APL as a model system. |
| Keywords: | signal transduction; review; interferon; models, biological; relapse; drug synergism; disease model; leukemia, promyelocytic, acute; gene expression regulation, neoplastic; cytokine; acute myeloblastic leukemia; hematopoietic cell; remission induction; molecular biology; cell nucleus receptor; retinoic acid; leukemia cell line; leukemia remission; acute promyelocytic leukemia; pml/rarα; p21(waf1/cip1); retinoic acid receptor; tretinoin; pml; chromosome translocation 17; interferons; humans; human; priority journal; chromosome translocation 15; irf-1; stat-1 |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 30 |
| Issue: | 1-2 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 1998-01-01 |
| Start Page: | 11 |
| End Page: | 22 |
| Language: | English |
| PUBMED: | 9669672 |
| PROVIDER: | scopus |
| DOI: | 10.3109/10428199809050925 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 12 December 2016 -- Source: Scopus |
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