Understanding the molecular pathogenesis of acute promyelocytic leukemia

Francesco Lo-Coco, Syed Khizer Hasan

Research output: Contribution to journalArticle

Abstract

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).

Original languageEnglish
Pages (from-to)3-9
Number of pages7
JournalBest Practice and Research: Clinical Haematology
Volume27
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • DNA damage
  • mouse models
  • non-homologous end joining
  • PML-RARα
  • t-APL

ASJC Scopus subject areas

  • Oncology
  • Clinical Biochemistry
  • Medicine(all)

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