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Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 195...

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Autores principales: McCulloch, Derek, Brown, Christina, Iland, Harry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359123/
https://www.ncbi.nlm.nih.gov/pubmed/28352191
http://dx.doi.org/10.2147/OTT.S100513
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author McCulloch, Derek
Brown, Christina
Iland, Harry
author_facet McCulloch, Derek
Brown, Christina
Iland, Harry
author_sort McCulloch, Derek
collection PubMed
description Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms. Both are characterized by a balanced translocation between the long arms of chromosomes 15 and 17, [t(15;17)(q24;q21)], giving rise to a unique fusion gene PML-RARA and an abnormal chimeric transcription factor (PML-RARA), which disrupts normal myeloid differentiation programs. The success of current treatments for APL is in marked contrast to the vast majority of patients with non-promyelocytic AML. The overall prognosis in non-promyelocytic AML is poor, and although there has been an improvement in overall survival in patients aged <60 years, only 30%–40% of younger patients are still alive 5 years after diagnosis. APL therapy has diverged from standard AML therapy through the empirical discovery of two agents that directly target the molecular basis of the disease. The evolution of treatment over the last 4 decades to include all-trans retinoic acid and arsenic trioxide, with chemotherapy limited to patients with high-risk disease, has led to complete remission in 90%–100% of patients in trials and rates of overall survival between 86% and 97%.
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spelling pubmed-53591232017-03-28 Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives McCulloch, Derek Brown, Christina Iland, Harry Onco Targets Ther Review Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms. Both are characterized by a balanced translocation between the long arms of chromosomes 15 and 17, [t(15;17)(q24;q21)], giving rise to a unique fusion gene PML-RARA and an abnormal chimeric transcription factor (PML-RARA), which disrupts normal myeloid differentiation programs. The success of current treatments for APL is in marked contrast to the vast majority of patients with non-promyelocytic AML. The overall prognosis in non-promyelocytic AML is poor, and although there has been an improvement in overall survival in patients aged <60 years, only 30%–40% of younger patients are still alive 5 years after diagnosis. APL therapy has diverged from standard AML therapy through the empirical discovery of two agents that directly target the molecular basis of the disease. The evolution of treatment over the last 4 decades to include all-trans retinoic acid and arsenic trioxide, with chemotherapy limited to patients with high-risk disease, has led to complete remission in 90%–100% of patients in trials and rates of overall survival between 86% and 97%. Dove Medical Press 2017-03-14 /pmc/articles/PMC5359123/ /pubmed/28352191 http://dx.doi.org/10.2147/OTT.S100513 Text en © 2017 McCulloch et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
McCulloch, Derek
Brown, Christina
Iland, Harry
Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives
title Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives
title_full Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives
title_fullStr Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives
title_full_unstemmed Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives
title_short Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives
title_sort retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359123/
https://www.ncbi.nlm.nih.gov/pubmed/28352191
http://dx.doi.org/10.2147/OTT.S100513
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