Mechanism of action of retinoids in a new therapeutic approach to acute promyelocytic leukemia

摘要: Vitamin A (retinol) and retinoic acid, its natural derivative, play an important role in the growth, differentiation development of known normal tissues. Retinoids have recently become interest to research areas as diverse dermatology, embryonal cancer research. Retinol is major retinoid transported blood tissues by specific carrier retinol binding protein (RBP). The level plasma regulated very precisely homeostasis. RBP-retinol circulation supplies target cells, which then activate into acid (RA) if they possess NAD-dependent enzymatic oxidation system. RA, one most active metabolites retinol, also present low concentration RA rate formation varies from depending on need cell. cellular transport biological activity retinoids may be mediated their cytoplasmic proteins (CRBP) (CRABP) function shuttles targetting nucleosol fraction and/or regulator RA. nuclear RARs (retinoic receptors), are members receptor superfamily likely final transducers signal at gene expression. All-trans (ATRA) able specifically differentiate malignant cells leukemic patients with APL short-term culture. For this reason, were successfully treated ATRA (Chinese French results). Acute promyelocytic leukemia M3 (French-American-British FAB classification) a rare disease (10% AML), characterized reciprocal chromosome 15-17 translocation. It has been shown that 17 breakpoint translocation localized within RAR alpha gene. Due t(15;17) translocated PML 15 resulting synthesis PML/RAR fusion messenger RNA. Detection transcript now molecular marker disease. abnormal exhibits altered transcription activation properties when compared alpha. Clinical trials demonstrated extremely efficient inducing complete remission patients. morphologic finding maturing elements bone marrow peripheral during treatment indicates obtained without hypoplasia suggests differentiating mechanism involved.(ABSTRACT TRUNCATED AT 400 WORDS)