CD36 cell surface expression as a surrogate marker to identify ABL/JAK-class kinase fusions in pediatric BCP-ALL.

Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. Most cases with ABL-class fusion are classified as high-risk yet display good responses to tyrosine kinase inhibitors (TKIs). Current clinical protocols recommend adding a TKI to chemotherapy as soon as possible, making it mandatory to rapidly identify these alterations.

Sexuality- and Fertility-Related Issues in Women after Allogeneic Hematopoietic Stem Cell Transplantation.

Sexual dysfunction and fertility related issues appear as major post-allogeneic hematopoietic stem cell transplantation (HSCT) late effects in young women, with a heavy impact on quality of life. The objective of the present study was to evaluate the impact of disease and treatments on sexual quality of life, ovarian function, and family planning initiatives in the context of allogeneic HSCT. Between January 2014 and January 2016, adult female patients who underwent HSCT before age 35 and had been followed for more than 2 years in our center were offered participation in the study through a self-reported survey and/or ovarian function assessment if age <40 at inclusion.

Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma.

Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance.

Classic and Variants APLs, as Viewed from a Therapy Response.

Most acute promyelocytic leukemia (APL) are caused by PML-RARA, a translocation-driven fusion oncoprotein discovered three decades ago. Over the years, several other types of rare X-RARA fusions have been described, while recently, oncogenic fusion proteins involving other retinoic acid receptors (RARB or RARG) have been associated to very rare cases of acute promyelocytic leukemia. PML-RARA driven pathogenesis and the molecular basis for therapy response have been the focus of many studies, which have now converged into an integrated physio-pathological model.

Human Hepatocytes and Differentiated Adult-Derived Human Liver Stem/Progenitor Cells Display Immunosuppressive Properties Mediated, at Least in Part, through the Nonclassical HLA Class I Molecule HLA-G.

One of the main challenges in liver cell therapy (LCT) is the induction of a tolerogenic microenvironment to promote graft acceptance in the recipient. Little is known about the immunomodulatory potential of the hepatic cells used in liver cell therapy. In this work, we wanted to evaluate the immunosuppressive properties of human hepatocytes and adult-derived human liver stem/progenitor cells (ADHLSCs), as well as the potential involvement of the immunomodulatory molecule HLA-G.

SIU-ICUD on bladder cancer: pathology.

Many changes have been made during these last years and concepts for understanding bladder cancer have evolved. We make an update with the latest findings of the WHO (World Health Organistaion) 2016, ICCR (International Collaboration on Cancer Reporting) and other official organisms and try to show the latest developments. In this document we provide new consensus guidelines and insights.

Lect2 Controls Inflammatory Monocytes to Constrain the Growth and Progression of Hepatocellular Carcinoma.

Leukocyte cell-derived chemotaxin-2 (LECT2) was originally identified as a hepatocyte-secreted chemokine-like factor and a positive target of β-catenin signaling. Here, we dissected out the mechanisms by which LECT2 modulates hepatocellular carcinoma (HCC) development using both HCC mouse models and human HCC samples. We have demonstrated that LECT2 exhibits dual abilities as it has profound repercussions on the tumor phenotype itself and the immune microenvironment.

Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection.

HIV-1 mutations rapidly accumulate through genetic recombination events, which require the infection of a single cell by two virions (coinfection). Accumulation of mutations in the viral population may lead to immune escape and high-level drug resistance. The existence of cell subpopulations characterized by different susceptibility to HIV-1 infection has been proposed as an important parameter driving coinfection (Dang et al.

Chromatin mobility upon DNA damage: state of the art and remaining questions.

Chromosome organization and chromatin mobility are central to DNA metabolism. In particular, it has been recently shown by several labs that double strand breaks (DSBs) in yeast induce a change in chromatin mobility at the site of the damage. Intriguingly, DSB also induces a global mobility of the genome, at others, potentially undamaged positions.

Dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.

Retinoic acid (RA) and arsenic target the t(15;17)(q24;q21) PML/RARA driver of acute promyelocytic leukemia (APL), their combination now curing over 95% patients. We report exome sequencing of 64 matched samples collected from patients at initial diagnosis, during remission, and following relapse after historical combined RA-chemotherapy treatments. A first subgroup presents a high incidence of additional oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis.

Clinical relevance of mutant allele burden during follow-up in acute myeloid leukemia. A study by the French ALFA group.

Assessment of minimal residual disease has emerged as a powerful prognostic factor in acute myeloid leukemia. In this study, we investigated the potential of mutations as targets for minimal residual disease assessment in acute myeloid leukemia, since these mutations collectively occur in 15-20% of cases of acute myeloid leukemia and now represent druggable targets. We employed droplet digital polymerase chain reaction assays to quantify , , and mutations on genomic DNA in 322 samples from 103 adult patients with primary mutant acute myeloid leukemia and enrolled on Acute Leukemia French Association (ALFA) - 0701 or -0702 clinical trials.

From dynamic chromatin architecture to DNA damage repair and back.

Maintaining the integrity of the genome in the face of DNA damage is crucial to ensure the survival of the cell and normal development. DNA lesions and repair occur in the context of the chromatin fiber, whose 3D organization and movements in the restricted volume of the nucleus are under intense scrutiny. Here, we highlight work from our and other labs that addresses how the dynamic organization of the chromatin fiber affects the repair of damaged DNA and how, conversely, DNA damage and repair affect the structure and dynamics of chromatin in the budding yeast nucleus.

aCNViewer: Comprehensive genome-wide visualization of absolute copy number and copy neutral variations.

Motivation: Copy number variations (CNV) include net gains or losses of part or whole chromosomal regions. They differ from copy neutral loss of heterozygosity (cn-LOH) events which do not induce any net change in the copy number and are often associated with uniparental disomy. These phenomena have long been reported to be associated with diseases and particularly in cancer.

Number of infection events per cell during HIV-1 cell-free infection.

HIV-1 accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution.

Chromatin stiffening underlies enhanced locus mobility after DNA damage in budding yeast.

DNA double-strand breaks (DSBs) induce a cellular response that involves histone modifications and chromatin remodeling at the damaged site and increases chromosome dynamics both locally at the damaged site and globally in the nucleus. In parallel, it has become clear that the spatial organization and dynamics of chromosomes can be largely explained by the statistical properties of tethered, but randomly moving, polymer chains, characterized mainly by their rigidity and compaction. How these properties of chromatin are affected during DNA damage remains, however, unclear.

Epidemiology of invasive fungal infections during induction therapy in adults with acute lymphoblastic leukemia: a GRAALL-2005 study.

Little data have been published concerning invasive fungal infections during treatment of acute lymphoblastic leukemia (ALL). Patients included between May 2006 and October 2012 in the multicenter phase III trial for newly diagnosed ALL (GRAALL-2005) were retrospectively reviewed for the occurrence of IFI using the EORTC modified criteria. These patients did not routinely receive antifungal prophylaxis.

Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma.

We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24.

Toward understanding and exploiting tumor heterogeneity.

The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized.

HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary of recent achievements.

For the past decade protein acetylation has been shown to be a crucial post-transcriptional modification involved in the regulation of protein functions. Histone acetyltransferases (HATs) mediate acetylation of histones which results in the nucleosomal relaxation associated with gene expression. The reverse reaction, histone deacetylation, is mediated by histone deacetylases (HDACs) leading to chromatin condensation followed by transcriptional repression.