Involvement of PML proteins in treatment of acute promyelocytic leukemia with arsenic trioxide.
- Author:
Rui HAO
1
;
Lide SU
1
;
Yiming SHAO
1
;
Na BU
2
;
Liya MA
3
;
Hua NARANMANDURA
1
Author Information
1. Department of Pharmacology, Inner Mongolia Medical University, Hohhot 010000, China.
2. Department of Pharmacy, Woman's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
3. Department of Hematology, the First Affiliate Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
therapeutic use;
Arsenic Trioxide;
therapeutic use;
Drug Resistance, Neoplasm;
genetics;
Humans;
Leukemia, Promyelocytic, Acute;
drug therapy;
Mutation;
Oncogene Proteins, Fusion;
metabolism;
Promyelocytic Leukemia Protein;
chemistry;
genetics;
metabolism
- From:
Journal of Zhejiang University. Medical sciences
2018;47(5):541-551
- CountryChina
- Language:Chinese
-
Abstract:
Promyelocytic leukemia (PML) protein, a tumor suppressor, plays an important role in patients with acute promyelocytic leukemia (APL) receiving arsenic trioxide (AsO) therapy. APL is a M3 subtype of acute myeloid leukemia (AML), which is characterized by expression of PML-RARα (P/R) fusion protein, leading to the oncogenesis. AsO is currently used as the first-line drug for patients with APL, and the mechanism may be:AsO directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Gene mutations may lead to relapse and drug resistance after AsO treatment. In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with AsO; and explain how PML protein mutations could cause resistance to AsO therapy.
