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].

Understanding the molecular pathogenesis of acute promyelocytic leukemia

LO COCO, FRANCESCO;
2014

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).
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - Malattie del Sangue
English
DNA damage; PML–RARα; mouse models; non-homologous end joining; t-APL; Animals; Antineoplastic Agents; Arsenicals; Cell Differentiation; Cell Transformation, Neoplastic; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Clinical Trials as Topic; DNA End-Joining Repair; Disease Models, Animal; Drug Synergism; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Mice; Molecular Targeted Therapy; Neoplasm Proteins; Neoplasms, Second Primary; Neoplastic Stem Cells; Oncogene Proteins, Fusion; Oxides; Signal Transduction; Topoisomerase II Inhibitors; Tretinoin; Translocation, Genetic
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].
LO COCO, F; Hasan, S
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/160487
Citazioni
  • ???jsp.display-item.citation.pmc??? 22
  • Scopus 52
  • ???jsp.display-item.citation.isi??? 47
social impact