PI3-kinase deletion promotes myelodysplasia by dysregulating autophagy in hematopoietic stem cells.

Myelodysplastic syndrome (MDS) is a clonal malignancy arising in hematopoietic stem cells (HSCs). The mechanisms of MDS initiation in HSCs are still poorly understood. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is frequently activated in acute myeloid leukemia, but in MDS, PI3K/AKT is often down-regulated.

The balance between the intronic miR-342 and its host gene Evl determines hematopoietic cell fate decision.

Protein-coding and non-coding genes like miRNAs tightly control hematopoietic differentiation programs. Although miRNAs are frequently located within introns of protein-coding genes, the molecular interplay between intronic miRNAs and their host genes is unclear. By genomic integration site mapping of gamma-retroviral vectors in genetically corrected peripheral blood from gene therapy patients, we identified the EVL/MIR342 gene locus as a hotspot for therapeutic vector insertions indicating its accessibility and expression in human hematopoietic stem and progenitor cells.

PI3 kinase alpha and delta promote hematopoietic stem cell activation.

Many cytokines and chemokines that are important for hematopoiesis activate the PI3K signaling pathway. Because this pathway is frequently mutated and activated in cancer, PI3K inhibitors have been developed for the treatment of several malignancies, and are now being tested in the clinic in combination with chemotherapy. However, the role of PI3K in adult hematopoietic stem cells (HSCs), particularly during hematopoietic stress, is still unclear.

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.

Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation.

The effect of sortilin silencing on ovarian carcinoma cells.

Background: Our preliminary data on the protein expression of SORT1 in ovarian carcinoma tissues showed that sortilin was overexpressed in ovarian carcinoma patients and cell lines, while non-malignant ovaries expressed comparably lower amount of this protein. In spite of diverse ligands and also different putative functions of sortilin (NTR3), the function of overexpressed sortilin in ovarian carcinoma cells is an intriguing subject of inquiry. The aim of this study was, therefore, to investigate the functional role of sortilin in survival of ovarian carcinoma cell line.

EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.

Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec).

Indoleamine 2,3-dioxygenase (IDO) is expressed at feto-placental unit throughout mouse gestation: An immunohistochemical study.

Introduction: The cells expressing Indoleamine 2, 3-dioxygenase (IDO) in feto-maternal interface mediate tryptophan catabolism, hence protect allogeneic fetus from lethal rejection by maternal immune responses. In this study, we report immuno-localization of IDO(+) cells in murine reproductive tract and placenta throughout mouse pregnancy by immunohistochemistry.

Materials And Methods: Syngeneic pregnant mice were examined for vaginal plug to discover about their state of pregnancy.

Ectopic Expression of Sortilin 1 (NTR-3) in Patients with Ovarian Carcinoma.

Gene expression profiling of ovarian carcinoma tissues has shown an increase of four-fold expression of SORT1 gene. Sortilin 1 (NTR-3) is a 95-100 kDa protein normally expressed in heart, brain, placenta, skeletal muscle, spinal cord, thyroid, and testis. However, its expression has never been reported in normal ovary.