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Differentiation therapy of acute myeloid leukemia: past, present and future.

Petrie, Kevin, Zelent, Arthur and Waxman, Samuel (2009) Differentiation therapy of acute myeloid leukemia: past, present and future. Current opinion in hematology, 16 (2). pp. 84-91. ISSN 1531-7048

Item Type: Article

Abstract

PURPOSE OF REVIEW

Since the 1970s, the concept of differentiation therapy has been viewed as a promising and revolutionary approach for the treatment of acute myeloid leukemia (AML) and other cancers. However, the successful clinical application of differentiation therapy has only been realized since the late 1980s and only in one subtype of AML, acute promyelocytic leukemia (APL). The use of all-trans-retinoic acid (ATRA) and arsenic trioxide, both of which induce degradation of the progressive multifocal leukoencephalopathy/retinoic acid receptor alpha oncoprotein, in combination with chemotherapy is currently the accepted treatment of APL, presenting a potential paradigm for differentiation therapy in clinical oncology.

RECENT FINDINGS

We have begun to understand why ATRA fails to induce differentiation in AML. The underlying reasons identified thus far are associated with an inability to target the removal of leukemogenic fusion proteins, aberrant epigenetic regulation of genes involved in the ATRA signaling pathway and the presence of factors that interfere with proper retinoic acid receptor alpha function.

SUMMARY

Here, we examine the reasons why the exquisite sensitivity of APL to ATRA-based differentiation therapy has not been extended to other of AML subtypes. Current differentiation-based combinatorial approaches to target AML will also be analyzed. Finally, we will evaluate the potential of novel strategies, high-throughput screening, and functional genomics to uncover new differentiation-based therapies for AML.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12432
Identification Number: https://doi.org/10.1097/MOH.0b013e3283257aee
ISSN: 1531-7048
URI: http://sure.sunderland.ac.uk/id/eprint/12432
Official URL: https://journals.lww.com/co-hematology/Abstract/20...

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 17:56
Last Modified: 30 Sep 2020 10:48

Contributors

Author: Kevin Petrie ORCID iD
Author: Arthur Zelent
Author: Samuel Waxman

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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