Hematopoiesis News Volume 4.38 | Oct 1 2013

Retinoic Acid Signaling Is Essential for Embryonic Hematopoietic Stem Cell Development
Scientists showed that activation of retinoic acid (RA) signaling in aorta-gonad-mesonephros-derived hemogenic endothelium ex vivo dramatically enhanced its hematopoietic stem cell (HSC) potential, whereas conditional inactivation of the RA metabolizing enzyme retinal dehydrogenase 2 in VE-cadherin expressing endothelial cells in vivo abrogated HSC development. [Cell] Abstract | Graphical Abstract

Notchless-Dependent Ribosome Synthesis Is Required for the Maintenance of Adult Hematopoietic Stem Cells
Researchers identified Notchless (Nle) as a critical factor for hematopoietic stem cell (HSC) maintenance under both homeostatic and cytopenic conditions. Nle deficiency leads to a rapid and drastic exhaustion of HSCs and immature progenitors and failure to maintain quiescence in HSCs. [J Exp Med] Abstract

The Role, Mechanism and Potentially Therapeutic Application of MicroRNA-29 Family in Acute Myeloid Leukemia
Investigators report that the family members, miR-29a, -29b and -29c, were commonly downregulated in peripheral blood mononuclear cells and bone marrow CD34+ cells derived from acute myeloid leukemia patients as compared with the healthy donors. Overexpression of each miR-29 member in THP1 and NB4 cells markedly inhibited cell proliferation and promoted cell apoptosis. [Cell Death Differ] Abstract

Prevention of Graft-versus-Host-Disease with Preserved Graft-versus-Leukemia-Effect by Ex Vivo and In Vivo Modulation of CD4+ T-Cells
Scientists showed that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG₁ simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect) and the long-term suppression of the deleterious side effect Graft-versus-host-disease. [Cell Mol Life Sci] Abstract

Top-Down Motif Engineering of a Cytokine Receptor for Directing Ex Vivo Expansion of Hematopoietic Stem Cells
The authors engineered a tyrosine motif located in the intracellular domain of scFv-thrombopoietin receptor chimera (S-Mpl) based on a top-down approach in order to change the signaling properties of the chimera. The truncated mutant and an amino-acid substitution mutant (Q to L) of S-Mpl were constructed to investigate the ability of these mutants to expand hematopoietic stem cells. [J Biotechnol] Abstract

CLINICAL RESEARCH

Autologous Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Achieves Outcomes Similar to Allogeneic Transplantation – Results of CALGB Study 10001 (Alliance)
Scientists hypothesized that imatinib plus sequential chemotherapy will result in significant leukemia cell cytoreduction in patients with Philadelphia chromosome positive acute lymphoblastic leukemia, allowing collection of normal hematopoietic stem cells uncontaminated by residual BCR/ABL1+ lymphoblasts and thus reduce the likelihood of relapse after autologous stem cell transplantation for patients less than 60 years old without sibling donors. [Haematologica] Abstract | Full Article

Comparison of Intravenous with Oral Busulfan in Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Regimens for Pediatric Acute Leukemia
Researchers retrospectively analyzed 460 children with intravenous busulfan or oral busulfan receiving hematopoietic stem cell conditioning transplantation with busulfan-based myeloablative conditioning for acute leukemia. [Biol Blood Marrow Transplant] Abstract

Association between Busulfan Exposure and Outcome in Children Receiving Intravenous Busulfan before Hematopoietic Stem Cell Transplantation
Investigators evaluated the relation between steady-state concentration of busulfan (Bu) and clinical outcomes in children receiving Bu before hematopoietic stem cell transplantation. [Ther Drug Monit] Abstract

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Canadian Stem Cell Technology Expected to Offer New Options for Blood Stem Cell Transplants
A Canadian technology that has the potential to boost the number of stem cells given to patients undergoing transplants of the blood-forming system has been recognized as the most impactful stem cell research paper authored by a Canadian in the past year. Dr. Peter Zandstra has been given the 2013 Till & McCulloch Award in recognition of this contribution to global stem cell research. [Stem Cell Network] Press Release

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Faculty Positions – Stem Cells and Regenerative Medicine (Baylor College of Medicine)

Postdoctoral Position – Cellular and Genetic Therapies for Hemoglobinopathies (Blood Systems Research Institute)

Research Associate – Leukemia & Stem Cell Biology (King’s College London)

Postdoctoral Fellow – Mechanisms that Regulate Stem Cell Self-Renewal Using Mouse Blood-Forming Stem Cells (Columbia University)

Postdoctoral Researcher – Hematopoietic and Malignant Stem Cells (Istanbul University Institute of Experimental Medicine)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Technologist – Mesenchymal Cell Research (STEMCELL Technologies Inc.)

Research Technologist – Cell Culture Media & Matrices (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

Quality Control Analyst – Media (STEMCELL Technologies Inc.)

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