Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients.

The tyrosine kinase Inhibitor (TKI) imatinib is approved for the treatment of the chronic phase of chronic myeloid leukemia (CP-CML). Pharmacokinetic studies have highlighted the importance of inter-patient variability on imatinib plasma trough concentrations (ima[C]min). In the OPTIM-imatinib trial, we demonstrated that therapeutic drug monitoring (TDM) is able to improve the molecular response of CP-CML patients treated with imatinib.

Endothelial CD34 expression and regulation of immune cell response in-vitro.

Endothelial cells cover the lining of different blood vessels and lymph nodes, and have major functions including the transport of blood, vessel homeostasis, inflammatory responses, control of transendothelial migration of circulating cells into the tissues, and formation of new blood vessels. Therefore, understanding these cells is of major interest. The morphological features, phenotype and function of endothelial cells varies according to the vascular bed examined.

Inhibition of the PI3K/AKT/mTOR signaling promotes an M1 macrophage switch by repressing the ATF3-CXCL8 axis in Ewing sarcoma.

Ewing sarcomas are aggressive pediatric tumors of bone and soft tissues driven by in frame chromosomal translocations that yield fusion proteins guiding the oncogenic program. Promising alternative strategies to ameliorate current treatments involve inhibition of the PI3K/AKT/mTOR pathway. In this study, we identified the activating transcription factor 3 (ATF3) as an important mediator of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.

Biomaterial-embedded extracellular vesicles improve recovery of the dysfunctional myocardium.

Extracellular vesicles (EV) are increasingly recognized as a therapeutic option in heart failure. They are usually administered by direct intramyocardial injections with the caveat of a rapid wash-out from the myocardium which might weaken their therapeutic efficacy. To improve their delivery in the failing myocardium, we designed a system consisting of loading EV into a clinical-grade hyaluronic acid (HA) biomaterial.

The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.

Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step.

Extracellular vesicles fail to trigger the generation of new cardiomyocytes in chronically infarcted hearts.

Extracellular vesicles (EV) mediate the therapeutic effects of stem cells but it is unclear whether this involves cardiac regeneration mediated by endogenous cardiomyocyte proliferation. Bi-transgenic MerCreMer/ZEG (n = 15/group) and Mosaic Analysis With Double Markers (MADM; n = 6/group) mouse models underwent permanent coronary artery ligation and received, 3 weeks later, 10 billion EV (from human iPS-derived cardiovascular progenitor cells [CPC]), or saline, injected percutaneously under echo guidance in the peri-infarcted myocardium. Endogenous cardiomyocyte proliferation was tracked by EdU labeling and biphoton microscopy.

BET inhibitors impair leukemic stem cell function only in defined oncogenic subgroups of acute myeloid leukaemias.

Bromodomain and Extra-Terminal inhibitors (BETi) such as OTX015 are active in Acute Myeloid Leukaemias (AML). Their activity on Leukemic Stem Cells (LSCs) is less documented. We interrogated the anti-LSC activity of OTX015 in a niche-like long-term culture in 26 primary AML samples and validated our findings in vivo.

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients.

To evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements.

Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis.

The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127 and CD127 early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127 and CD127 ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials.

An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.

Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation.

Mutation in TET2 in myeloid cancers.

Background: The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. The mechanisms underlying these disorders are not well defined.

Methods: We conducted a combination of molecular, cytogenetic, comparative-genomic-hybridization, and single-nucleotide-polymorphism analyses to identify a candidate tumor-suppressor gene common to patients with myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia (AML).

Assessing the potential leukemogenic effects of 50 Hz magnetic fields and their harmonics using an animal leukemia model.

To answer the still unresolved question of the possible leukemogenic effects of extremely low frequency magnetic fields (ELF-MFs) and of their harmonics on the incidence of B acute lymphoblastic leukemia in children, we used an animal model to explore the possible co-initiating or co-promoting effects of ELF-MFs on the development of leukemia. We used a rat model in which B acute lymphoblastic leukemia is chemically induced by a nitrosurea derivative. From the onset of the chemical treatment, the animals were also exposed to ELF-MFs (100 microT, sinusoidal 50 Hz MFs), with or without harmonics.

Progesterone receptor availability in mouse spermatozoa during epididymal transit and capacitation: ligand blot detection of progesterone-binding protein.

The goals of the present study were to determine the availability of progesterone (P4) receptor (P4r) in mouse sperm during maturation and capacitation and to make the first steps toward a characterization of P4r. It has been proposed that P4 is able to induce an acrosomal reaction (AR) by using a membrane P4r. This induction was verified in sperm isolated from the cauda epididymis (fully mature) when incubated in specific conditions that capacitate sperm.