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  • Title: Phenotypic reversion in acute promyelocytic leukemia.
    Author: Degos L.
    Journal: Nouv Rev Fr Hematol (1978); 1991; 33(6):511-5. PubMed ID: 1667950.
    Abstract:
    Acute promyelocytic leukemia (APL) is a clonal expansion of malignant cells blocked at a specific stage of myeloid differentiation. The disease is associated with a specific translocation between chromosome 17 and chromosome 15 t (15; 17) and with a bleeding diathesis previously attributed to a disseminated intravascular coagulation which is recently also related to a primary fibrinolysis. The high percentage of early deaths, around 20% experienced by APL patients, is generally due to the haemorrhagic syndrome. A new feature is the highly effectiveness of all-trans retinoic acid treatment, a vitamin A derivative, for inducing complete remission in patients. The induction of cellular maturation by this agent represents the first model of differentiation therapy. Furthermore recent molecular studies revealed that the breakpoints of the t(15; 17) translocation are clustered in the gene of retinoic acid receptor a, generating a hybrid gene product. Gene transfection experiments disclosed the impairment of gene transactivation due to the hybrid gene products, opening new concepts for the leukemogenesis. The abnormal program made by the aberrant transcript might be overcome by pharmacological concentration of RA which induces an over expression of the normal allele and a normal activity of the aberrant product.
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