Acute promyelocytic leukemia (APL) cells, containing the t(15;17) rearrangement, express the fusion protein, PML/ RARa. Clinically, patients respond to all-trans retinoic acid (ATRA) through complete remissions associated with myeloid maturation of leukemic cells. This clinical ATRA response of APL is linked to PML/RARa expression. Unfortunately, these remissions are transient and relapsed APL ...

Expression of the PML-retinoic acid receptor (PML-RAR ) fusion protein is the initiating genetic event for acute promyelocytic leukemia (APL), but the molecular mechanisms responsible for disease initiation are not yet clear. Several observations have suggested that early myeloid cells are uniquely susceptible to transformation by PML-RAR . Recently, we have shown that the early myeloid-specifi...

morphology and other phenotypic features characteristic of cellular senescence can be triggered by telomere attrition (replicative senescence) and various stresses such as activated oncogenes or genotoxic treatments (premature senescence). Physiological relevance of cellular senescence is apparent from its emerging roles in aging, in tumor pathogenesis as an inducible barrier to tumor progressi...

We investigated delay in diagnosing progressive multifocal leukoencephalopathy (PML). The median time from initial symptom to diagnosis was 74 days (range 1-1643) in 111 PML patients seen at our institution from 1993 to 2015. Another diagnosis was considered before PML in nearly two-thirds, and more than three-quarters of patients suffered from diagnostic delay greater than 1 month, irrespectiv...

The perfectly matched layer (PML) was first introduced by Berenger as a material absorbing boundary condition (ABC) for electromagnetic waves. In this paper, a method is developed to extend the perfectly matched layer to simulating seismic wave propagation in poroelastic media. This nonphysical material is used at the computational edge of a finite-difference algorithm as an ABC to truncate unb...

Arsenic trioxide chemotherapy cures acute promyelocytic leukemia by inducing the ubiquitylation of an oncogenic fusion protein containing promyelocytic leukemia protein (PML) subsequent to modification of PML by SUMO1 and SUMO2. We proposed that the SUMO switch at Lys(65) of PML enhanced subsequent SUMO2 conjugation to Lys(160) and consequent RNF4-dependent ubiquitylation of PML. Ferhi et al no...

BACKGROUND The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV). OBJECTIVE To describe the 12-month clinic...

Partial multi-label learning (PML), which tackles the problem of prediction models from instances with overcomplete noisy annotations, has recently started gaining attention research community. In this paper, we propose a novel adversarial model, PML-GAN, under generalized encoder-decoder framework for partial learning. The PML-GAN model uses disambiguation network to identify irrelevant labels...

Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17)(q22;q21) involving the PML and RARA genes is associated with exposure to agents targeting topoisomerase II (topoII), particularly mitoxantrone and epirubicin. We previously have shown that mitoxantrone preferentially induces topoII-mediated DNA damage in a "hotspot region" within PML intron 6. To investigate mechanisms underlyin...

Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated P...