Hematopoiesis News Volume 5.07 | Feb 25 2014

Cytotoxic CD8⁺ T Cells Stimulate Hematopoietic Progenitors by Promoting Cytokine Release from Bone Marrow Mesenchymal Stromal Cells
Scientists showed that interferon γ secreted by effector cytotoxic CD8⁺ T cells stimulates hematopoiesis at the level of early multipotent hematopoietic progenitor cells and induces myeloid differentiation. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release

Identification of Small Molecules that Support Human Leukemia Stem Cell Activity Ex Vivo
Currently available culture conditions do not prevent spontaneous differentiation of leukemic stem cells (LSCs), which greatly limits the feasibility of cell-based assays. To overcome these constraints investigators conducted a high-throughput chemical screen and identified small molecules that inhibit differentiation and support LSC activity in vitro. [Nat Methods] Abstract

Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
Researchers report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia that they treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. [Sci Transl Med] Abstract | Press Release

Haploinsufficiency of Sf3b1 Leads to Compromised Stem Cell Function but Not to Myelodysplasia
Scientists investigated the functional role of SF3B1 in normal hematopoiesis utilizing Sf3b1 heterozygous deficient mice. Sf3b1^+/- mice had a significantly reduced number of hematopoietic stem cells (CD34^–cKit⁺ScaI⁺Lin^– cells) compared with Sf3b1^+/+ mice, but hematopoiesis was grossly normal in Sf3b1^+/- mice. [Leukemia] Abstract

Identification of Renin Progenitors in the Mouse Bone Marrow that Give Rise to B-Cell Leukemia
Scientists showed that the bone marrow contains a progenitor that expresses renin throughout development and possesses a B-lymphocyte pedigree. This cell requires RBP-J to differentiate. Deletion of RBP-J in these renin-expressing progenitors enriches the precursor B-cell gene program and constrains lymphocyte differentiation, facilitated by H3K4me3 activating marks in genes that control the pre-B stage. [Nat Commun] Full Article

Endothelial Smad4 Restrains the Transition to Hematopoietic Progenitors via Suppression of ERK Activation
Researchers showed that genetic deletion of Smad4 from the endothelium stage (using Tie2-Cre), but not from embryonic hematopoietic cells (using Vav-Cre), leads to a strikingly augmented emergence of intra-arterial hematopoietic clusters and an enhanced in vitro generation of hematopoietic progenitors, with no increase in the proliferation and survival of hematopoietic cluster cells. [Blood] Abstract

PI3K p110δ Uniquely Promotes Gain-of-Function Shp2-Induced GM-CSF Hypersensitivity in a Model of Juvenile Myelomonocytic Leukemia
Using genetic models, scientists demonstrate that inactivation of phosphatidylinositol-3-kinase (PI3K) catalytic subunit, p110δ, but not PI3K p110α, corrects gain-of-function Shp2-induced GM-CSF hypersensitivity, Akt and Erk hyperactivation, and skewed hematopoietic progenitor distribution. [Blood] Abstract

E3-Ligase Skp2 Regulates β-Catenin Expression and Maintains Hematopoietic Stem Cell Homing
Scientists showed that S-phase kinase associated protein2 (Skp2) was a novel and critical regulator for maintaining the homing of hematopoietic stem cells as well as their residence in the endosteal niche. [Biochem Biophys Res Commun] Abstract

CLINICAL RESEARCH

Predictive Factors for the Outcome of Allogeneic Transplantation in Patients with Myelodysplastic Syndrome Stratified According to the Revised International Prognostic Scoring System (IPSS-R)
To identify predictive factors for transplantation outcome, investigators studied 519 patients with myelodysplastic syndrome or oligoblastic acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation and were reported to the GITMO registry between 2000 and 2011. [Blood] Abstract

Prognostic Index for Relapsed Acute Leukemia after Allogeneic Stem Cell Transplantation
Researchers retrospectively studied patients who relapsed after allogeneic stem cell transplantation (SCT) to identify factors influencing outcomes. Of the 296 patients, 102 experienced relapse at a median of 222 days after SCT. [Leuk Lymphoma] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.

Teva Announces Full FDA Approval of SYNRIBO^® (Omacetaxine Mepesuccinate) for Injection
Teva Pharmaceutical Industries Ltd. announced that the U.S. Food and Drug Administration (FDA) has granted full approval of SYNRIBO^® for injection. SYNRIBO is indicated for adult patients with chronic phase or accelerated phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. [Teva Pharmaceutical Industries Ltd.] Press Release

From our sponsor:
View immunology lectures, protocols and other resources on the Human Immunology Portal.

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

Visit our events page to see a complete list of events in the hematopoiesis research community.

Postdoctoral Position – Genes that Regulate Hematopoietic Stem Cells (University of Chicago)

Postdoctoral Fellow – Erythropoiesis and Iron Metabolism (University of Wisconsin – Madison)

Postdoctoral Position – Hematopoietic Stem Cell Biology (St. Jude Children’s Research Hospital)

Postdoctoral Positions – New Models of Hematopoiesis and Hematopoietic Disorders (Mount Sinai Medical Center)

Assistant Professorship – Hematopoietic Stem Cells and Microenvironment (University of Zurich)

Postdoctoral Fellow – Hematopoietic Stem Cell and Leukemia Research (City of Hope)

Postdoctoral Position – Hematopoietic Stem Cell Physiology and Bone Marrow Failure (University of Michigan)

Research Associate – Normal & Leukemic Stem Cells (King’s College London)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

Scientific Affairs Coordinator (American Society of Hematology)

Postdoctoral Position – Erythroid and Myeloid Differentiation of Hematopoietic Stem Cells (Imagine Institute)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

Recruit Top Talent: Reach more than 50,000 potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.