ABSTRACT
The leukaemia-associated fusion gene, promyelocytic leukaemia (PML)-retinoic acid receptor-a (RARa), causes acute promyelocytic leukaemia (APL) by blocking differentiation and increasing self-renewal of leukaemic progenitor cells. The current standard of APL’s induction therapy comprises all-trans retinoic acid and chemotherapy, but arsenic trioxide also cures many patients and is used routinely in the treatment of relapsed patients. Importantly, all diagnostic tests take advantage of the presence of this unique chromosomal translocation in APL and its product - PML/RARa fusion gene. Twenty-years on from the original cloning of PML/RARa, it is clear that careful studies of disease pathogenesis are fundamental for devising efficient molecular target-based therapies. The expression of PML/RARa is critical for the transformation of haematopoietic stem cells and/or progenitors in vitro and causes leukaemia in transgenic murine models that faithfully recapitulates the features of the human malignancy. The classical phenotypes associated with PML/RARa expression include the block of differentiation and the promotion of survival or self-renewal.
