An ATRActive future for differentiation therapy in AML

Daniel E Johnson; Robert L Redner

doi:10.1016/j.blre.2015.01.002

An ATRActive future for differentiation therapy in AML

Blood Rev. 2015 Jul;29(4):263-8. doi: 10.1016/j.blre.2015.01.002. Epub 2015 Jan 21.

Authors

Daniel E Johnson¹, Robert L Redner²

Affiliations

¹ Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh PA 15213 USA.
² Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh PA 15213 USA. Electronic address: redner@pitt.edu.

Abstract

The success of all-trans retinoic acid (ATRA) therapy in acute promeylocytic leukemia (APL) has spawned numerous attempts to translate the paradigm of differentiation therapy to non-APL acute myelocytic leukemia (AML). However, the results of clinical trials have been overall disappointing. In this review we discuss the mechanism of retinoic acid signaling and the results of major clinical trials that have attempted to incorporate ATRA into AML regimens. We discuss recent evidence that indicate that the retinoic acid signaling pathway may be dysfunctional in AML. Preliminary studies suggest that targeting the pathways that modify retinoic acid receptor activity may reactivate the dormant retinoic acid-signaling pathway. Such strategies may revive the ability of ATRA to induce myeloid differentiation and apoptosis in non-APL AML.

Keywords: AML; ATRA; differentiation therapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / therapeutic use*
Apoptosis
Cell Differentiation
Humans
Leukemia, Myeloid, Acute / drug therapy*
Signal Transduction
Tretinoin / therapeutic use*

Substances

Antineoplastic Agents
Tretinoin

Grants and funding

P30 CA047904/CA/NCI NIH HHS/United States