• B Acad Nat Med Paris · Jan 1998

    Review

    [Arsenic and retinoic acid, towards targeted treatments of acute promyelocytic leukemia?].

    • H de Thé.
    • CNRS UPR 9051, Hôpital St. Louis, Paris.
    • B Acad Nat Med Paris. 1998 Jan 1; 182 (1): 63-71.

    AbstractAcute promyelocytic leukaemia is a key model system in cancer biology. Its exquisite sensitivity to retinoic acid constitutes the first example of differentiation therapy. The PML/RAR alpha fusion protein generated by the t(15; 17) translocation is the molecular basis of transformation. PML/RAR alpha induces transformation most likely through a dominant negative interference with the function of nuclear receptors leading to a differentiation block. The fusion protein also delocalizes PML and other nuclear body antigens and this alteration of nuclear protein traffic seems to play a role in growth control and apoptosis. The clinical response of this disease to retinoids and arsenic trioxide, both of which induce the degradation of the fusion protein, constitute the first example of a therapy directly targeted to a specific genetic lesion in a human cancer.

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