Rational targeting in acute promyelocytic leukemia Journal Article
| Author: | Papanikolaou, N. A. |
| Article Title: | Rational targeting in acute promyelocytic leukemia |
| Abstract: | Acute promyelocytic leukemia (ARL) is characterized by the nearly homogeneous expression of the fusion oncogenic protein PML-RARα and the testis-specific cyclin A1 protein, which are implicated in its pathogenesis. PML-RARα binds all-trans retinoic acid with high affinity inducing granulocytic differentiation and remission. Current approaches with high doses of single or combined all-trans retinoic acid and chemotherapeutic agents, though relatively efficacious in the beginning, are highly toxic with severe side-effects (retinoic acid syndrome) and are followed by relapse in a high proportion of patients. Here it is proposed that targeting APL with low levels of all-trans retinoic acid combined with small molecule inhibitors of cyclin-dependent kinases may have the potential to be equally or more efficacious as any of the current single or combined agent approaches, affording reduced toxicity and relapse rates. |
| Keywords: | protein expression; drug efficacy; nonhuman; antineoplastic agents; recurrence risk; antineoplastic combined chemotherapy protocols; cell differentiation; dose-response relationship, drug; drug resistance, neoplasm; carcinogenesis; drug delivery systems; leukemia, promyelocytic, acute; hybrid protein; drug mechanism; enzyme inhibitors; promyelocytic leukemia; hematopoietic cell; cell cycle arrest; cyclin-dependent kinases; cyclin dependent kinase inhibitor; retinoic acid; drug protein binding; granulocyte; differentiation; promyelocytic leukemia protein; retinoic acid receptor alpha; acute myeloid leukemia (aml); acute promyelocytic leukemia (apl); all-trans retinoic acid (atra); ccaat/enhancer binding protein epsilon (c/ebpε); cyclin a1; cyclin a2 (a2); cyclin dependent-kinase 1 (cdk1); cyclin dependent-kinase 2 (cdk2); pml-rarα; promyelocyte (pm); promyelocytic leukemia zinc finger protein (plzf); retinoic acid receptor α (rarα); rexinoid acid receptor (rxr); tretinoin |
| Journal Title: | In Vivo |
| Volume: | 24 |
| Issue: | 1 |
| ISSN: | 0258-851X |
| Publisher: | International Institute of Anticancer Research |
| Date Published: | 2010-01-01 |
| Start Page: | 21 |
| End Page: | 27 |
| Language: | English |
| PUBMED: | 20133971 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: IVIVE" - "Source: Scopus" |
