LABORATORY RESEARCH DNA Methylation of Runx1 Regulatory Regions Correlates with Transition from Primitive to Definitive Hematopoietic Potential In Vitro and In Vivo The authors investigated DNA methylation of known Runx1 cis-elements at stages of hematopoietic development in vivo, and during differentiation of murine embryonic stem cells in vitro. They found at the distal promoter, loss of methylation correlated with the primitive to definitive transition in vivo. [Blood] Abstract Growth Factor Independent-1 Maintains Notch1-Dependent Transcriptional Programming of Lymphoid Precursors Scientists showed that immature hematopoietic cells require Growth factor independent 1 (Gfi1) to competently integrate Notch-activated signaling. Notch1 activation coupled with Gfi1 deficiency early in T-lineage specification leads to a dramatic loss of T-cells, whereas activation in later stages leaves development unaffected. [PLoS Genet] Full Article Expression of Podocalyxin Separates the Hematopoietic and Vascular Potentials of Mouse ES Cell-Derived Mesoderm Researchers report that surface expression of Podocalyxin (Podxl), a member of the CD34 family of sialomucins, can be used to subdivide the Flk1+ cells in differentiating embryoid bodies at day 4.75 into populations that develop into distinct mesodermal lineages. Definitive hematopoietic potential was restricted to the Flk1+Podxl+ population, while the Flk1-negative Podxl+ population displayed only primitive erythroid potential. [Stem Cells] Abstract Loss of Quiescence and Impaired Function of CD34+/CD38low Cells One Year Following Autologous Stem Cell Transplantation Bone marrow primitive progenitor cells were examined one year following autologous stem cell transplantation and compared with normal bone marrow and mobilized peripheral blood stem cells. Post-transplantation bone marrow contained a significant lower percentage of quiescent cells in the CD34+/CD38low fraction compared to normal bone marrow. [Haematologica] Abstract | Full Article Characterization of Regulatory Dendritic Cells that Mitigate Acute Graft-versus-Host Disease in Older Mice Following Allogeneic Bone Marrow Transplantation Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease graft-versus-host disease-associated mortality. To evaluate this approach in older BMT recipients, young (3-4 months) and older (14-18 months) DCreg were generated using GM-CSF, IL-10, and TGFβ. [PLoS One] Full Article Drosophila E-Cadherin Functions in Hematopoietic Progenitors to Maintain Multipotency and Block Differentiation Scientists showed that E-cadherin is an important regulator of prohemocyte fate choice, maintaining prohemocyte multipotency and blocking differentiation. These functions are reminiscent of the role of E-cadherin in mammalian embryonic stem cells. [PLoS One] Full Article GSK-3β Inhibition Preserves Naïve T Cell Phenotype in Bone Marrow Reconstituted Mice Investigators demonstrated that GSK-3β inhibitor, 6-bromoindirubin 3′-oxime, activates Wingless/β-catenin signaling, elevates the proportion of naïve T cells and delays T cell differentiation during homeostatic T cell expansion in lymphodepleted mice transplanted with human hematopoietic stem cells. [Exp Hematol] Abstract Active RHOA Favors Retention of Human Hematopoietic Stem/Progenitor Cells in Their Niche By utilizing constitutively active and dominant negative RHOA, scientists showed that RHOA negatively regulates both in vitro and in vivo migration and dominant negative RHOA significantly increased the migration potential of human hematopoietic stem/progenitor cells. [J Biomed Sci] Full Article CLINICAL RESEARCH CMV Serostatus Has Still an Important Prognostic Impact in De Novo Acute Leukemia Patients after Allogeneic Stem Cell Transplantation: A Report from the Acute Leukemia Working Party of EBMT Investigators analyzed the prognostic impact of donor and recipient cytomegalovirus (CMV) serostatus in 16628 de novo acute leukemia patients after allogeneic stem cell transplantation. In comparison to CMV-seronegative recipients allografted from a CMV-seronegative donor, cases with CMV seropositivity of the donor and/or the recipient showed a significantly decreased 2-year leukemia-free survival and overall survival, and increased non-relapse mortality. [Blood] Abstract An Intermediate Alemtuzumab Schedule Reduces the Incidence of Mixed Chimerism Following Reduced Intensity Conditioning Hematopoietic Cell Transplantation for Hemophagocytic Lymphohistiocytosis Researchers hypothesized that an intermediate alemtuzumab schedule would reduce mixed chimerism and maintain a low incidence of acute GVHD. Twenty-four consecutive transplants were performed in patients with hemophagocytic lymphohistiocytosis and related disorders using a novel intermediate alemtuzumab schedule of 1mg/kg beginning on day-14. [Biol Blood Marrow Transpl] Abstract |