Autophagy and Ubiquitin-Mediated Proteolytic Degradation of PML/Rarα Fusion Protein in Matrine-Induced Differentiation Sensitivity Recovery of ATRA-Resistant APL (NB4-LR1) Cells: in Vitro and in Vivo Studies.
Acute promyelocytic leukemia (APL) is characterized by the reciprocal translocation t(15;17)(q22;q21), resulting in the fusion of the promyelocytic leukemia gene at 15q22 with the retinoic acid receptor α at 17q21.
Among them, members of the tripartite motif (TRIM) family have emerged as important players endowed with both antiviral effects and modulatory capacity of the innate immune response.TRIM5α and TRIM19 (i.e. promyelocytic leukemia, PML) are among the best-characterized family members; however, in this review we will focus on the potential role of another family member, i.e.
<i>TBL1XR1-RARB</i> as an oncogenic protein exerts effects similar to those of <i>PML-RARA</i>, underpinning the importance of retinoic acid pathway alterations in the pathogenesis of APL.<b>Significance:</b> These findings report a novel and distinct genetic subtype of acute promyelocytic leukemia (APL) by illustrating that the majority of APL without RARA translocations harbor RARB translocations.<i></i>.
Several host gene products, including the nuclear domain 10 (ND10) components PML (promyelocytic leukemia) and Daxx (death domain-associated protein 6), as well as IFI16 (interferon-inducible protein 16), have been shown to restrict herpes simplex virus 1 (HSV-1) replication.
Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year.
Acute promyelocytic leukemia (APL) is a subtype of acute leukemia characterized by a unique t(15;17) translocation generating the PML/RARA fusion gene and hybrid oncoprotein.
Human acute promyelocytic leukemia (APL) cells are characterized by the arrest of differentiation at the promyelocytic stage due to epigenetic perturbations induced by PML/RARα fusion protein (Promyelocytic Leukemia protein - PML/Retinoic Acid Receptor alpha - RARα).
Of 84 cases (63%) that lacked monocytic differentiation ("myeloid AML"), 40 (48%) demonstrated an acute promyelocytic leukemia-like (APL-like) immunophenotype by flow cytometry, with absence of CD34 and HLA-DR and strong myeloperoxidase expression, in the absence of a PML-RARA translocation.
Our current data strongly indicate that PAO has good effects on the mutant PML protein solubility changes, and it may be helpful for improving the therapeutic strategies for arsenic-resistant APL treatments in the near future.
Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia.
Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene.
Notably, pharmacological inhibition of PML with arsenic trioxide, a PML-degrading agent used to treat promyelocytic leukemia patients, delays tumor growth, impairs TNBC metastasis, and cooperates with chemotherapy by preventing metastatic dissemination.
In the majority of acute promyelocytic leukemia (APL) cases, translocons produce a promyelocytic leukemia protein-retinoic acid receptor α (PML-RARα) fusion gene.