Understanding the molecular pathogenesis of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) associated with peculiar biologic and clinical features and requiring specific management. At the genetic level, APL is featured by a unique chromosome translocation t(15;17) which results in the PML-RARα gene fusion and chimeric protein. APL is the first example of differentiation therapy targeted to a defined genetic target i.e. PML-RARα. PML-RARα behaves as an altered retinoic acid receptor with an ability of transmitting oncogenic signaling leading to accumulation of undifferentiated promyelocytes. All-trans-retinoic acid (ATRA) induces disease remission in APL patients by triggering terminal differentiation of leukemic promyelocytes. More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARα oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Elucidating the oncogenic signaling of PML-RARα through various transcription factors and the study of APL mouse models have greatly helped to understand the molecular pathogenesis of APL. However, the precise molecular mechanism by which t(15;17) is formed and initiates leukemia remains unknown. While transforming oncogenic potential of PML-RARα has been described extensively, the mechanistic events important for the formation of t(15;17) have been taken from the model of Therapy-related APL (t-APL).

Lo-Coco F ，Hasan SK 《-》

Retinoic acid (RA) and As2O3 treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARalpha and PLZF-RARalpha oncoproteins.

Rego EM ，He LZ ，Warrell RP Jr ，Wang ZG ，Pandolfi PP ... -  《-》

Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells.

Zheng X ，Seshire A ，Rüster B ，Bug G ，Beissert T ，Puccetti E ，Hoelzer D ，Henschler R ，Ruthardt M ... -  《-》

The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic leukemia.

Jing Y 《-》

Characterisation of the PML/RAR alpha rearrangement associated with t(15;17) acute promyelocytic leukaemia.

Grimwade D ，Solomon E 《Current Topics in Microbiology and Immunology》