All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells. Issue 20 (17th October 2020)

• Record Type: Journal Article
• Authors: Nguyen, Chi H.; Grandits, Alexander M.; Purton, Louise E.; Sill, Heinz; Wieser, Rotraud
• Is Part Of: Cell cycle. Volume 19:Issue 20(2020)
• Page Start: 2573
• Page End: 2588
• Publication Date: 2020-10-17
• Subjects: AML -- atRA -- hematopoietic stem cell -- leukemia stem cell -- MECOM -- FLT3; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2020.1810402
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive, often fatal hematopoietic malignancy. All-trans retinoic acid (atRA), one of the first molecularly targeted drugs in oncology, has greatly improved the outcome of a subtype of AML, acute promyelocytic leukemia (APL). In contrast, atRA has so far provided little therapeutic benefit in the much larger group of patients with non-APL AML. Attempts to identify genetically or molecularly defined subgroups of patients that may respond to atRA have not yielded consistent results. Since AML is a stem cell-driven disease, understanding the effectiveness of atRA may require an appreciation of its impact on AML stem cells. Recent studies reported that atRA decreased stemness of AML with an FLT3 -ITD mutation, yet increased it in AML1-ETO driven or EVI1 -overexpressing AML. This review summarizes the role of atRA in normal hematopoiesis and in AML, focusing on its impact on AML stem cells.