Pleiotrophin Mediates Hematopoietic Regeneration via Activation of RAS Scientists found that systemic administration of pleiotrophin (PTN), a protein that is secreted by BM-derived endothelial cells, substantially increased the survival of mice following radiation exposure and after myeloablative BM transplantation. In both models, PTN increased survival by accelerating the recovery of BM hematopoietic stem and progenitor cells in vivo. [J Clin Invest] Full Article Hematopoietic RIPK1 Deficiency Results in Bone Marrow Failure Caused by Apoptosis and RIPK3-Mediated Necroptosis To identify the lineages and cell types that depend on receptor-interacting serine/threonine-protein kinase 1 (RIPK1) for survival, scientists generated conditional Ripk1 mice. Tamoxifen administration to adult RosaCreERT2Ripk1fl/fl mice resulted in lethality caused by cell death in the intestinal and hematopoietic lineages. [Proc Natl Acad Sci USA] Abstract Persistence of Virus Reservoirs in ART-Treated SHIV-Infected Rhesus Macaques after Autologous Hematopoietic Stem Cell Transplant Researchers performed autologous hematopoietic stem cell transplantation (HSCT) in three Simian/Human Immunodeficiency Virus (SHIV)-infected, antiretroviral therapy (ART)-treated rhesus macaques using HSCs collected prior to infection and compared them to three SHIV-infected, ART-treated, untransplanted control animals to assess the effect of conditioning and autologous HSCT on viral persistence. [PLoS Pathog] Full Article | Press Release Single-Cell Analyses of Regulatory Network Perturbations Using Enhancer-Targeting TALEs Suggest Novel Roles for PU.1 during Hematopoietic Specification Numerous transcription factors (TFs), including Scl and PU.1, are known regulators of developmental and adult hematopoiesis, but how they act within wider TF networks is still poorly understood. Researchers report transcription activator-like effectors (TALEs) engineered to target the PU.1-14kb and Scl+40kb transcriptional enhancers as efficient new tools to perturb the expression of these key hematopoietic TFs. [Development] Abstract | Full Article Circadian and Circannual Variations in Cord Blood Hematopoietic Cell Composition The authors observed that gestational age, birth weight and baby’s gender impacted concentrations of nucleated and hematopoietic progenitor cells in cord blood. They also show that uses of epidural anesthesia and of oxytocin were associated with higher concentrations of hematopoietic progenitor cells. [Haematologica] Abstract | Full Article Directed Differentiation of Embryonic Stem Cells Using a Bead-Based Combinatorial Screening Method The authors describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which they discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. [PLoS One] Full Article | Press Release Sall4 Overexpression Blocks Murine Hematopoiesis in a Dose-Dependent Manner Scientists show that Sall4b is the predominant isoform in murine hematopoietic stem cells (HSCs) and progenitors. Overexpression of either Sall4a or Sall4b in HSCs or progenitors impairs hematopoietic colony formation and expansion in vitro. [Exp Hematol] Abstract CLINICAL RESEARCH Delayed Hematopoietic Recovery after Auto-SCT in Patients Receiving Arsenic Trioxide-Based Therapy for Acute Promyelocytic Leukemia: A Multi-Center Analysis Researchers retrospectively reviewed the clinical histories of 58 patients undergoing autologous hematopoietic SCT for acute promyelocytic leukemia at 21 institutions in the United States and Japan. Thirty-three of the patients received arsenic-based therapy prior to stem cell collection. [Bone Marrow Transplant] Abstract A Phase I Study of the Safety, Pharmacokinetics, and Anti-Leukemic Activity of the Anti-CD123 Monoclonal Antibody, CSL360, in Relapsed, Refractory or High-Risk Acute Myeloid Leukemia (AML) AML blasts express high levels of IL-3 receptor-α (CD123). CSL360 is a recombinant, chimeric IgG1, anti-CD123 monoclonal antibody that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. Investigators assessed safety, pharmacokinetics and bioactivity of weekly IV CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels. [Leuk Lymphoma] Abstract |