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, S.K. (2014). Understanding the molecular pathogenesis of acute promyelocytic leukemia. BAILLIERE'S BEST PRACTICE IN CLINICAL HAEMATOLOGY, 27(1), 3-9 [10.1016/j.beha.2014.04.006].
|Tipologia:||Articolo su rivista|
|Citazione:||Lo Coco, F., & Hasan, S.K. (2014). Understanding the molecular pathogenesis of acute promyelocytic leukemia. BAILLIERE'S BEST PRACTICE IN CLINICAL HAEMATOLOGY, 27(1), 3-9 [10.1016/j.beha.2014.04.006].|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.beha.2014.04.006|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2014|
|Titolo:||Understanding the molecular pathogenesis of acute promyelocytic leukemia|
|Autori:||Lo Coco, F; Hasan, SK|
|Appare nelle tipologie:||01 - Articolo su rivista|