Publisher Correction: Localization of RalB signaling at endomembrane compartments and its modulation by autophagy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Targeting Myeloperoxidase Disrupts Mitochondrial Redox Balance and Overcomes Cytarabine Resistance in Human Acute Myeloid Leukemia.

Chemotherapies alter cellular redox balance and reactive oxygen species (ROS) content. Recent studies have reported that chemoresistant cells have an increased oxidative state in hematologic malignancies. In this study, we demonstrated that chemoresistant acute myeloid leukemia (AML) cells had a lower level of mitochondrial and cytosolic ROS in response to cytarabine (AraC) and overexpressed myeloperoxidase (MPO), a heme protein that converts hydrogen peroxide to hypochlorous acid (HOCl), compared with sensitive AML cells.

Exploiting metabolic vulnerabilities for personalized therapy in acute myeloid leukemia.

Changes in cell metabolism and metabolic adaptation are hallmark features of many cancers, including leukemia, that support biological processes involved into tumor initiation, growth, and response to therapeutics. The discovery of mutations in key metabolic enzymes has highlighted the importance of metabolism in cancer biology and how these changes might constitute an Achilles heel for cancer treatment. In this Review, we discuss the role of metabolic and mitochondrial pathways dysregulated in acute myeloid leukemia, and the potential of therapeutic intervention targeting these metabolic dependencies on the proliferation, differentiation, stem cell function and cell survival to improve patient stratification and outcomes.

Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens.

CD38 is expressed in several types of non-Hodgkin lymphoma (NHL) and constitutes a promising target for antibody-based therapy. Daratumumab (Darzalex) is a first-in-class anti-CD38 antibody approved for the treatment of relapsed/refractory (R/R) multiple myeloma (MM). It has also demonstrated clinical activity in Waldenström macroglobulinaemia and amyloidosis.

Single-Cell Signature Explorer for comprehensive visualization of single cell signatures across scRNA-seq datasets.

The momentum of scRNA-seq datasets prompts for simple and powerful tools exploring their meaningful signatures. Here we present Single-Cell_Signature_Explorer (https://sites.google.

Molecular Inverse Comorbidity between Alzheimer's Disease and Lung Cancer: New Insights from Matrix Factorization.

Matrix factorization (MF) is an established paradigm for large-scale biological data analysis with tremendous potential in computational biology. Here, we challenge MF in depicting the molecular bases of epidemiologically described disease-disease (DD) relationships. As a use case, we focus on the inverse comorbidity association between Alzheimer's disease (AD) and lung cancer (LC), described as a lower than expected probability of developing LC in AD patients.

Localization of RalB signaling at endomembrane compartments and its modulation by autophagy.

The monomeric GTPase RalB controls crucial physiological processes, including autophagy and invasion, but it still remains unclear how this multi-functionality is achieved. Previously, we reported that the RalGEF (Guanine nucleotide Exchange Factor) RGL2 binds and activates RalB to promote invasion. Here we show that RGL2, a major activator of RalB, is also required for autophagy.

Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes.

γδ T lymphocytes represent ∼1% of human peripheral blood mononuclear cells and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current single-cell RNA sequencing (scRNA-seq) studies do not identify γδ T lymphocytes because their transcriptomes at the single-cell level are unknown. Here we show that high-resolution clustering of large scRNA-seq datasets and a combination of gene signatures allow the specific detection of human γδ T lymphocytes and identification of their T cell receptor (TCR)Vδ1 and TCRVδ2 subsets in large datasets from complex cell mixtures.

ChiCMaxima: a robust and simple pipeline for detection and visualization of chromatin looping in Capture Hi-C.

Capture Hi-C (CHi-C) is a new technique for assessing genome organization based on chromosome conformation capture coupled to oligonucleotide capture of regions of interest, such as gene promoters. Chromatin loop detection is challenging because existing Hi-C/4C-like tools, which make different assumptions about the technical biases presented, are often unsuitable. We describe a new approach, ChiCMaxima, which uses local maxima combined with limited filtering to detect DNA looping interactions, integrating information from biological replicates.

Identifying the reactive metabolites of tyrosine kinase inhibitors in a comprehensive approach: Implications for drug-drug interactions and hepatotoxicity.

Tyrosine kinase inhibitors (TKI) are small heterocyclic molecules targeting transmembrane and cytoplasmic tyrosine kinases that have met with considerable success in clinical oncology. TKI are associated with toxicities including liver injury that may be serious and even life-threatening. Many of them require warnings in drug labeling against liver injury, and five of them have Black Box Warning (BBW) labels.

Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma.

Purpose: The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification.

Multiparametric analysis of CD8 T cell compartment phenotype in chronic lymphocytic leukemia reveals a signature associated with progression toward therapy.

CD8 T cells are frontline defenders against cancer and primary targets of current immunotherapies. In CLL, specific functional alterations have been described in circulating CD8 T cells, yet a global view of the CD8 T cell compartment phenotype and of its real impact on disease progression is presently elusive. We developed a multidimensional statistical analysis of CD8 T cell phenotypic marker expression based on whole blood multi-color flow-cytometry.

PTMselect: optimization of protein modifications discovery by mass spectrometry.

Discovery of protein modification sites relies on protein digestion by proteases and mass spectrometry (MS) identification of the modified peptides. Depending on proteases used and target protein sequence, this method yields highly variable coverage of modification sites. We introduce PTMselect, a digestion-simulating software which tailors the optimal set of proteases for discovery of global or targeted modification from any single or multiple proteins.

Boosting γδ T cell-mediated antibody-dependent cellular cytotoxicity by PD-1 blockade in follicular lymphoma.

Follicular lymphoma (FL) is a common non Hodgkin's lymphoma subtype in which immune escape mechanisms are implicated in resistance to chemo-immunotherapy. Although molecular studies point to qualitative and quantitative deregulation of immune checkpoints, in depth cellular analysis of FL immune escape is lacking. Here, by functional assays and analyses we show that a subset of FL patients displays a 'high' immune escape phenotype.

Selective Targeting of the Interconversion between Glucosylceramide and Ceramide by Scaffold Tailoring of Iminosugar Inhibitors.

A series of simple -alkyl pyrrolidines already known as cytotoxic inhibitors of ceramide glucosylation in melanoma cells can be converted into their corresponding 6-membered analogues by means of a simple ring expansion. This study illustrated how an isomerisation from iminosugar pyrrolidine toward piperidine could invert their targeting from glucosylceramide (GlcCer) formation toward GlcCer hydrolysis. Thus, we found that the 5-membered ring derivatives did not inhibit the hydrolysis reaction of GlcCer catalysed by lysosomal β-glucocerebrosidase (GBA).

Pharmacokinetic interaction between mitotane and etoposide in adrenal carcinoma: a pilot study.

Background The combination of mitotane and platinum-etoposide chemotherapy is a front-line treatment in metastatic adrenocortical carcinoma (ACC), although this regimen shows limited efficacy. Pharmacokinetic drug-drug interaction between mitotane, a strong CYP3A4 inducer, and etoposide, which is a substrate of CYP3A4, may contribute to chemoresistance. The aim of this pilot study was to assess the pharmacokinetic interaction between mitotane and etoposide in ACC patients.

Elaboration of a thermosensitive smart biomaterial: From synthesis to the ex vivo bioadhesion evaluation.

Alginate and chitosan are polysaccharides that are widely used in the biomedical field, especially as wound dressings. Controlled bioadhesion is an advanced functionality that offers the potential to reduce injuries due to the stripping-off of the biomaterial. Herein, we report the efficient grafting of poly-N(isopropylacryamide) (PNIPAM), a thermosensitive polymer that exhibits a lower critical solution temperature (LCST) at 32 °C on the alginate/chitosan polyelectrolyte complex (PEC) surface.

Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas.

BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAF-mutant melanoma cell-autonomous resistance to BRAFi.

How can we best monitor 5-FU administration to maximize benefit to risk ratio?

5-Fluorouracil (5-FU) is currently used as a chemotherapy in several cancers such as head-and-neck (H&N) and colorectal cancers. 5-FU dosing is traditionally based on body surface area (BSA), but this strategy is usually associated with severe toxicities. 5-FU is mainly catabolized by dihydropyrimidine dehydrogenase (DPD), and 5-FU dosage adaptation according to DPD status at the first cycle of treatment is now recommended.

Profiling Immune Escape in Hodgkin's and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining.

Therapeutic blockade of PD-1/PD-L1 shows promising results in Hodgkin's lymphoma (HL) and in some diffuse large B-cell lymphoma (DLBCL) patients, but biomarkers predicting such responses are still lacking. To this end, we recently developed a transcriptional scoring of immune escape (IE) in cancer biopsies. Using this method in DLBCL, we identified four stages of IE correlated with overall survival, but whether Hodgkin's lymphomas (HL) also display this partition was unknown.

Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia.

: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells.

Myeloma MRD by deep sequencing from circulating tumor DNA does not correlate with results obtained in the bone marrow.

There is no correlation between ctDNA and bone marrow for MRD by NGS using only immunoglobulin gene rearrangements in myeloma patients.