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Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.
- Source :
-
Cold Spring Harbor perspectives in medicine [Cold Spring Harb Perspect Med] 2024 Sep 03; Vol. 14 (9). Date of Electronic Publication: 2024 Sep 03. - Publication Year :
- 2024
-
Abstract
- Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion oncoprotein. Over the years, it has emerged as a model system to understand how this simple (and sometimes sole) genetic alteration can transform hematopoietic progenitors through the acquisition of dominant-negative properties toward both transcriptional control by nuclear receptors and PML-mediated senescence. The fortuitous identification of two drugs, arsenic trioxide (ATO) and all- trans -retinoic acid (ATRA), that respectively bind PML and RARA to initiate PML/RARA degradation, has allowed an unprecedented dissection of the cellular and molecular mechanisms involved in patients' cure by the ATO/ATRA combination. This analysis has unraveled the dual and complementary roles of RARA and PML in both APL initiation and cure by the ATRA/ATO combination. We discuss how some of the features unraveled by APL studies may be more broadly applicable to some other forms of leukemia. In particular, the functional synergy between drugs that promote differentiation and those that initiate apoptosis/senescence to impede self-renewal could pave the way to novel curative combinations.<br /> (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)
- Subjects :
- Humans
Receptors, Retinoic Acid metabolism
Receptors, Retinoic Acid genetics
Retinoic Acid Receptor alpha metabolism
Retinoic Acid Receptor alpha genetics
Promyelocytic Leukemia Protein metabolism
Promyelocytic Leukemia Protein genetics
Transcription Factors metabolism
Transcription Factors genetics
Leukemia, Promyelocytic, Acute drug therapy
Leukemia, Promyelocytic, Acute genetics
Tretinoin therapeutic use
Tretinoin pharmacology
Arsenic Trioxide pharmacology
Arsenic Trioxide therapeutic use
Oxides pharmacology
Oxides therapeutic use
Arsenicals pharmacology
Arsenicals therapeutic use
Oncogene Proteins, Fusion genetics
Oncogene Proteins, Fusion metabolism
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2157-1422
- Volume :
- 14
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cold Spring Harbor perspectives in medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38503502
- Full Text :
- https://doi.org/10.1101/cshperspect.a041582