Acute promyelocytic leukemia (APL) is characterized by expression of promyelocytic leukemia (PML)/retinoic acid (RA) receptor A (RARA) protein and all-trans-RA-mediated clinical remissions. RA treatment can confer PML/RARA degradation, overcoming dominant-negative effects of this oncogenic protein. The present study uncovered independent retinoid degradation mechanisms, targeting different doma...

The promyelocytic leukemia (PML) protein has been implicated in many cellular pathways, but it is unclear whether the accumulation of PML and other proteins into PML nuclear bodies is a regulated or random process. In this paper we have used a variety of physiological stresses, including heat stress, Cd+2 exposure and adenovirus E1A expression, as tools to study the principles underlying the as...

The tumor suppressor promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha in patients suffering from acute promyelocytic leukemia (APL). Treatment of APL patients with arsenic trioxide (As2O3) reverses the disease phenotype by a process involving the degradation of the fusion protein via its PML moiety. Several PML isoforms are generated from a single PML gene by al...

Recent reports suggest that human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) may improve with highly active antiretroviral therapy (HAART). We observed three patients who developed PML while receiving HAART. All patients received HAART for 4-11 months and had low plasma levels of HIV-1 RNA before the onset of symptoms of PML. Antiretroviral therapy ...

Several pathways have been implicated in the establishment of antiviral state in response to interferon (IFN), one of which implicates the promyelocytic leukemia (PML) protein. The PML gene has been discovered 20 years ago and has led to new insights into oncogenesis, apoptosis, cell senescence, and antiviral defense. PML is induced by IFN, leading to a marked increase of expression of PML isof...

Arsenic is a clinically effective treatment for acute promyelocytic leukaemia (APL) in which the promyelocytic leukaemia (PML) protein is fused to retinoic receptor alpha (RARα). PML-RARα is degraded by the proteasome by a SUMO-dependent, ubiquitin-mediated pathway in response to arsenic treatment, curing the disease. Six major PML isoforms are expressed as a result of alternative splicing, eac...

PML-RARA was proposed to initiate acute promyelocytic leukemia (APL) through PML-RARA homodimer-triggered repression. Here, we examined the nature of the PML-RARA protein complex and of its DNA targets in APL cells. Using a selection/amplification approach, we demonstrate that PML-RARA targets consist of two AGGTCA elements in an astonishing variety of orientations and spacings, pointing to hig...

Nuclear domain 10 (ND10), also referred to as nuclear bodies, are discrete interchromosomal accumulations of several proteins including promyelocytic leukemia protein (PML) and Sp100. In this study, we investigated the mechanism of ND10 assembly by identifying proteins that are essential for this process using cells lines that lack individual ND10-associated proteins. We identified the adapter ...

In anisotropic media, the standard perfectly matched layer (PML) technique suffers irrevocable instability in terminating unbounded problem domains. It remains an open question whether a stable PML-like absorbing boundary condition exists. For wave scattering layered orthotropic medium, this is affirmatively answered for first time paper. each permittivity tensor uniquely determines change of c...

Promyelocytic leukemia (PML) nuclear bodies selectively associate with transcriptionally active genomic regions, including the gene-rich major histocompatibility (MHC) locus. In this paper, we have explored potential links between PML and interferon (IFN)-γ-induced MHC class II expression. IFN-γ induced a substantial increase in the spatial proximity between PML bodies and the MHC class II gene...