Rapid Publication All-trans Retinoic Acid Modulates the Retinoic Acid Receptor-a in Promyelocytic Cells
نویسندگان
چکیده
We have recently demonstrated that all-trans retinoic acid (RA), the active metabolite of vitamin A, is an efficient alternative to chemotherapy in the treatment of acute promyelocytic leukemia (AML3). We have further shown that, in these AML3 cells, the gene of the retinoic acid receptor-a (RARa) is translocated from chromosome 17 to chromosome 15, and fused to a new gene, PLM. This results in the expression of both normal and chimeric RARa transcripts in AML3 cells. The PLM-RARa protein may account for the impairment of differentiation and thus leukemogenesis, but not for the paradoxical efficacy ofRA in these cells. In an attempt to elucidate RA's differentiative effect in AML3 patients, the present work examined the in vitro and in vivo modulation of the normal RARa transcripts by all-trans RA in seven cases of AML3. In all samples, Northern blot analysis revealed a low expression of the two normal RARa transcripts compared with other human myeloid leukemic cells. No modulation was observed after 4-8 d of in vivo therapy with all-trans RA 45 mg/m2 per d. In vitro incubation with all-trans RA, however, increased the level of expression of the normal RARa transcripts in AML3 cells but not in other AML leukemic subtypes. This modulation of the two normal RARa transcripts appeared to be an early and primary event of RA's differentiating effect. We therefore suggest that up-regulation of the normal RARa gene expression by pharmacological concentrations of all-trans RA may restore the normal differentiation pathway in these cells. (J. Clin. Invest. 1991. 88:2150-2154.)
منابع مشابه
تاثیر غلظتهای مختلف ال- ترانس رتینوئیک اسید بر رشد و بقای سلولهای بنیادی فولیکول موی موش سوری
Background and Objective: Hair follicle stem cells are multipotent, located in the bulge area, and are highly proliferating. Retinoids have an effect on epidermal differentiation and keratinization. Retinoic acid is used to treat some skin diseases such as Melasma, Acne and Ichthyosis. So, the study of all-trans retinoic acid effect on hair follicle stem cells and determination of the effective...
متن کاملAll-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway
متن کامل
Effects of novel retinoic acid compound, 9-cis-retinoic acid, on proliferation, differentiation, and expression of retinoic acid receptor-alpha and retinoid X receptor-alpha RNA by HL-60 cells.
Retinoic acid modulates proliferation and differentiation of a wide variety of normal and leukemic cells through two distinct families of transcriptional factors: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). A stereoisomer of retinoic acid, 9-cis-retinoic acid, is a high-affinity ligand for RXR and binds efficiently to RAR. In contrast, all-trans-retinoic acid interac...
متن کاملThe effect of bilateral intrahippocampal injection of all–trans retinoic acid on spatial learning in adult male rats.
Introduction: Previous studies have shown that vitamin A and its derivatives such as retinoid and all-trans retinoic acid have a crucial role in memory, learning and synaptic plasticity. The receptors of vitamin A are seen in different parts of the brain such as hippocampus, where vitamin A has an important role in learning. In this study, the effect of intrahippocampal (CA1) injection of al...
متن کاملRAPID COMMUNICATION Molecular Evaluation of Response to All-Trans-Retinoic Acid Therapy in Patients With Acute Promyelocytic Leukemia
The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short-lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor a (RARa) locus, which has recently been shown to be rearranged in all APLs. Southern blot analysis demonstrated that the RARa rearrangements persisted in the APL sampl...
متن کامل