Volume 4.42 | Oct 29

Hematopoiesis News 4.42 October 29, 2013
Hematopoiesis News
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Reduced-Intensity Conditioning and HLA-Matched Hemopoietic Stem-Cell Transplantation in Patients with Chronic Granulomatous Disease: A Prospective Multicenter Study
In chronic granulomatous disease, allogeneic hemopoietic stem-cell transplantation in adolescents and young adults and patients with high-risk disease is complicated by graft- failure, graft-versus-host disease, and transplant-related mortality. Researchers examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. [Lancet]
Abstract | Press Release

                                Take the if out of diff: Reduce variability when differentiating to hematopoietic cells
PUBLICATIONS ( Ranked by impact factor of the journal)

Niche-Based Screening Identifies Small-Molecule Inhibitors of Leukemia Stem Cells
Scientists screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared hematopoietic stem and progenitor cells was the cholesterol-lowering drug lovastatin. [Nat Chem Biol] Abstract

miR-142-3p Regulates the Formation and Differentiation of Hematopoietic Stem Cells in Vertebrates
Researchers showed that in zebrafish and mouse, miR-142-3p is specifically expressed in hematopoietic stem cells (HSCs). Knockdown of miR-142a-3p in zebrafish led to a reduced population of HSCs in the aorta-gonad-mesonephros region as well as T-cell defects in the thymus. [Cell Res] Abstract

Reprogramming of MLL-AF9 Leukemia Cells into Pluripotent Stem Cells
Researchers established an acute myeloid leukemia model by over-expressing the human mixed lineage leukemia AF9 (MLL-AF9) fusion gene in mouse hematopoietic cells that carry Yamanaka factors under the control of doxycycline (Dox). Upon addition of Dox in culture, the transplantable leukemia cells were efficiently converted into induced pluripotent stem cells that could form teratomas and produce chimeras. [Leukemia] Abstract | Full Article

Inhibition of Plasminogen Activator Inhibitor Type-1 Activity Enhances Rapid and Sustainable Hematopoietic Regeneration
The authors demonstrated that BM stromal cells, especially osteoblasts, produce PAI-1 in response to myeloablation, which negatively regulates the hematopoietic regeneration in the BM microenvironment. Genetic disruption of the PAI-1 gene, or pharmacological inhibition of PAI-1 activity, significantly improved the myeloablation-related mortality and promoted rapid hematopoietic recovery after hematopoietic stem cell transplantation through the induction of hematopoiesis-promoting factors. [Stem Cells] Abstract

Hematopoietic Expression of Oncogenic BRAF Promotes Aberrant Growth of Monocyte-Lineage Cells Resistant to PLX4720
Researchers generated a mouse model expressing inducible BRAFV600E in the hematopoietic system, and evaluated the efficacy of pathway-targeted therapeutics against primary hematopoietic cells. [Mol Cancer Res] Abstract

Nucleostemin Is Indispensable for the Maintenance and Genetic Stability of Hematopoietic Stem Cells
Scientists identified an indispensable role of nucleostemin in mouse hematopoietic stem cells (HSCs). Depletion of nucleostemin using short hairpin RNA strikingly impaired the self-renewal activity of HSCs both in vitro and in vivo. Consistently, nucleostemin depletion triggered apoptosis rather than cell-cycle arrest in HSCs. [Biochem Biophys Res Commun] Abstract


The Association of Cytochrome P450 Genetic Polymorphisms with Sulfolane Formation and the Efficacy of a Busulfan-Based Conditioning Regimen in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation
The authors explored the association between the cytochrome P450 (CYP)2C9, CYP2C19, CYP2B6 and flavin-containing monooxygenase3 genotypes and sulfolane (a water soluble metabolite of busulfan) plasma levels in children undergoing hematopoietic stem cell transplantation. The relationship between these genotypes and the effectiveness of myeloablative conditioning was also analyzed. [Pharmacogenomics J] Abstract

Favorable Impact of Pre-Transplant ATG on Outcomes of Reduced-Intensity Hematopoietic Cell Transplants from Partially Mismatched Unrelated Donors
Researchers performed a retrospective analysis of 85 patients who received unrelated donor transplants at their institution for hematologic malignancies following conditioning with fludarabine and melphalan, with or without rabbit antithymocyte globulin (ATG). [Bone Marrow Transplant] Abstract

Successful Rescue of Early Graft Failure in Pediatric Patients Using T-Cell-Depleted Haploidentical Hematopoietic SCT
Graft failure (GF) is a significant complication after allogeneic hematopoietic stem cell transplantation and is associated with a high mortality rate. The authors performed re-transplantation using haploidentical-related donors to rescue children with early GF. [Bone Marrow Transplant] Abstract

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Current and Future Approaches to Treat Graft Failure after Allogeneic Hematopoietic Stem Cell Transplantation
The authors summarize current approaches to treat graft failure/rejection after hematopoietic stem cell transplantation, and discuss new strategies of graft manipulation and immune therapy of particular interest for preventing/treating this complication. [Expert Opin Pharmacother] Abstract

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Senesco Opens New Clinical Trial Site at Seattle Cancer Care Alliance and Is Treating the First West Coast Patient
Senesco Technologies, Inc. reported the treatment of the first patient at the Company’s newly opened clinical-trial site at Seattle Cancer Care Alliance. This patient is part of Senesco’s Phase Ib/IIa clinical study of its therapeutic drug candidate, SNS01-T, targeting B-cell cancers. [Senesco Technologies, Inc.]
Press Release

STEMSOFT Licenses StemLab Software to TUMCells
STEMSOFT™ Software Inc. (STEMSOFT) announced the licensing of StemLab™, the leading cell therapy transplant laboratory software, to TUMCells Interdisziplinäres Zentrum für zelluläre Therapien Technische Universität München (TUMCells) at the University Hospital Klinikum rechts der Isar in Germany. [STEMSOFT Software Inc.] Press Release

STEMSOFT Announces Authorization to Submit Full Suite of AGNIS-Supported CIBMTR Forms
STEMSOFT™ Software Inc. (STEMSOFT) announced that the Center for International Blood & Marrow Transplant Research (CIBMTR®) has certified STEMSOFTconnect: REGISTRY to electronically submit all available forms using the CIBMTR AGNIS system. [STEMSOFT Software Inc.] Press Release

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Therapeutic Goods Administration (Australia)
NEW 40th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT)
September March 30-April 4, 2014
Milan, Italy

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NEW Postdoctoral Position – Transcriptional Regulation in Normal and Malignant Hematopoiesis (Karolinska Institutet)

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

Postdoctoral Position – Human Pluripotent and Hematopoietic Stem Cell Bioinformatics (Albert Einstein College Medicine)

Translational Clinician-Scientist – Stem Cell Transplantation (Boston Children’s Hospital)

Postdoctoral Research Fellow – Human Induced Pluripotent Stem Cell Research (Bioprocessing Technology Institute)

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

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

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

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

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

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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