Intensified immunosuppressive therapy in patients with immune checkpoint inhibitor-induced myocarditis.

Background: Myocarditis is a rare but life-threatening adverse event of cancer treatments with immune checkpoint inhibitors (ICIs). Recent guidelines recommend the use of high doses of corticosteroids as a first-line treatment, followed by intensified immunosuppressive therapy (IIST) in the case of unfavorable evolution. However, this strategy is empirical, and no studies have specifically addressed this issue.

Genomic trajectories to fluoroquinolone resistance in Francisella tularensis subsp. holarctica live vaccine strain.

Objectives: Fluoroquinolone (FQ)-resistant mutants were previously selected from the live vaccine strain (LVS) of Francisella tularensis (F. tularensis) subsp. holarctica.

Novel Intergenically Spliced Chimera, , Is Associated with Aggressive T-ALL Biology and Outcome.

Leukemias are frequently characterized by the expression of oncogenic fusion chimeras that normally arise due to chromosomal rearrangements. Intergenically spliced chimeric RNAs (ISC) are transcribed in the absence of structural genomic changes, and aberrant ISC expression is now recognized as a potential driver of cancer. To better understand these potential oncogenic drivers, high-throughput RNA sequencing was performed on T-acute lymphoblastic leukemia (T-ALL) patient specimens ( = 24), and candidate T-ALL-related ISCs were identified ( = 55; a median of 4/patient).

Homeobox protein TLX3 activates miR-125b expression to promote T-cell acute lymphoblastic leukemia.

The oncogenic mechanisms driven by aberrantly expressed transcription factors in T-cell acute leukemia (T-ALL) are still elusive. MicroRNAs (miRNAs) play an important role in normal development and pathologies. Here, we examined the expression of 738 miRNA species in 41 newly diagnosed pediatric T-ALLs and in human thymus-derived cells.

Transcriptional Profiling of Midguts Prepared from -Positive Collected from Two Distinct Cameroonian Foci: Coordinated Signatures of the Midguts' Remodeling As -Supportive Niches.

Our previous transcriptomic analysis of experimentally infected or not with aimed to detect differentially expressed genes (DEGs) associated with infection. Specifically, we selected candidate genes governing tsetse fly vector competence that could be used in the context of an anti-vector strategy, to control human and/or animal trypanosomiasis. The present study aimed to verify whether gene expression in field tsetse flies () is modified in response to natural infection by trypanosomes (), as reported when insectary-raised flies () are experimentally infected with .

Vorinostat and Mithramycin A in combination therapy as an interesting strategy for the treatment of Sézary T lymphoma: a transcriptomic approach.

SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and Drug Administration (FDA) for treating advanced refractory cutaneous T cell lymphomas. As SAHA alters the expression of many genes under control of the Sp1 transcription factor, we examined the effect of its association with the FDA-approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive inhibitor of Sp1 binding to DNA. Sézary syndrome (SS) cells, expanded ex vivo from peripheral blood mononuclear cells of 4 patients, were tested for their sensitivity to the drugs regarding cytotoxicity and differential responsive gene expression.

E2F transcription factors associated with up-regulated genes in glioblastoma.

Background: Glioblastoma is considered to the most common and malignant brain tumor in adults. Patients have a median survival of approximately one year from diagnosis due to poor response to therapy.

Objective: We applied bioinformatics approaches to predict transcription factors (TF) that are deregulated in glioblastoma in an attempt to point out molecular targets for therapy.

Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives.

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge.

Marseillevirus in lymphoma: a giant in the lymph node.

The family Marseilleviridae is a new clade of giant viruses whose original member, marseillevirus, was described in 2009. These viruses were isolated using Acanthamoeba spp primarily from the environment. Subsequently, a close relative of marseillevirus was isolated from the faeces of a healthy young man, and others were detected in blood samples of blood donors and recipients and in a child with lymph node adenitis.

Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia.

Unlabelled: Cancer onset and progression involves the accumulation of multiple oncogenic hits, which are thought to dominate or bypass the physiologic regulatory mechanisms in tissue development and homeostasis. We demonstrate in T-cell acute lymphoblastic leukemia (T-ALL) that, irrespective of the complex oncogenic abnormalities underlying tumor progression, experimentally induced, persistent T-cell receptor (TCR) signaling has antileukemic properties and enforces a molecular program resembling thymic negative selection, a major developmental event in normal T-cell development. Using mouse models of T-ALL, we show that induction of TCR signaling by high-affinity self-peptide/MHC or treatment with monoclonal antibodies to the CD3ε chain (anti-CD3) causes massive leukemic cell death.

[Cardiac pathologies and aging: lessons from a tiny heart].

The high level of conservation of the cardiogenic gene regulatory network as well as of the cellular and physiological characteristics of the cardiomyocytes between fly and human, makes the small heart of this invertebrate the simplest and most flexible genetic system to dissect the fundamental molecular mechanisms that are brought into play during the development, the establishment and the maintenance of the cardiac function. The recent improvements in techniques of measurements of cardiac function made it possible to validate Drosophila as a model of cardiomyopathies and arrhythmias of genetic and metabolic origin or dependent of ageing. The heart of the fly thus represents a model of choice to identify genes and their interactions implicated in cardiac pathologies.

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

Unlabelled: Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA-positive cases among 209 patients with adult T-cell acute lymphoblastic leukemia uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA-positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.

Dynamic recruitment of Ets1 to both nucleosome-occupied and -depleted enhancer regions mediates a transcriptional program switch during early T-cell differentiation.

Ets1 is a sequence-specific transcription factor that plays an important role during hematopoiesis, and is essential for the transition of CD4(-)/CD8(-) double negative (DN) to CD4(+)/CD8(+) double positive (DP) thymocytes. Using genome-wide and functional approaches, we investigated the binding properties, transcriptional role and chromatin environment of Ets1 during this transition. We found that while Ets1 binding at distal sites was associated with active genes at both DN and DP stages, its enhancer activity was attained at the DP stage, as reflected by levels of the core transcriptional hallmarks H3K4me1/3, RNA Polymerase II and eRNA.

Serum pantetheinase/vanin levels regulate erythrocyte homeostasis and severity of malaria.

Tissue pantetheinase, encoded by the VNN1 gene, regulates response to stress, and previous studies have shown that VNN genes contribute to the susceptibility to malaria. Herein, we evaluated the role of pantetheinase on erythrocyte homeostasis and on the development of malaria in patients and in a new mouse model of pantetheinase insufficiency. Patients with cerebral malaria have significantly reduced levels of serum pantetheinase activity (PA).

High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq.

Cell-type specific regulation of gene expression requires the activation of promoters by distal genomic elements defined as enhancers. The identification and the characterization of enhancers are challenging in mammals due to their genome complexity. Here we develop CapStarr-Seq, a novel high-throughput strategy to quantitatively assess enhancer activity in mammals.

Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo.

Hox proteins are well-established developmental regulators that coordinate cell fate and morphogenesis throughout embryogenesis. In contrast, our knowledge of their specific molecular modes of action is limited to the interaction with few cofactors. Here, we show that Hox proteins are able to interact with a wide range of transcription factors in the live Drosophila embryo.

Transcription-dependent generation of a specialized chromatin structure at the TCRβ locus.

V(D)J recombination assembles Ag receptor genes during lymphocyte development. Enhancers at AR loci are known to control V(D)J recombination at associated alleles, in part by increasing chromatin accessibility of the locus, to allow the recombination machinery to gain access to its chromosomal substrates. However, whether there is a specific mechanism to induce chromatin accessibility at AR loci is still unclear.

[Functions of lncRNA in development and diseases].

The transcription of essentially the entire eukaryotic genome generates a myriad of non-coding RNA species that show complex overlapping patterns of expression and regulation. In the last decade, several large scale genomic analyses have shed light on the widespread existence of long non-coding RNAs (lncRNAs) in mammals. Although the function of most lncRNAs remains unknown, many of them have been suggested to play important roles in the regulation of gene expression during normal development and diseases, including cancers.

RUNX1-dependent RAG1 deposition instigates human TCR-δ locus rearrangement.

V(D)J recombination of TCR loci is regulated by chromatin accessibility to RAG1/2 proteins, rendering RAG1/2 targeting a potentially important regulator of lymphoid differentiation. We show that within the human TCR-α/δ locus, Dδ2-Dδ3 rearrangements occur at a very immature thymic, CD34(+)/CD1a(-)/CD7(+dim) stage, before Dδ2(Dδ3)-Jδ1 rearrangements. These strictly ordered rearrangements are regulated by mechanisms acting beyond chromatin accessibility.