Hematopoiesis News Volume 4.44 | Nov 12 2013

CD133 Is a Positive Marker for a Distinct Class of Primitive Human Cord Blood-Derived CD34-Negative Hematopoietic Stem Cells
Using 18Lin^–CD34^– cells, scientists analyzed the expression of candidate positive markers by FCM. They finally identified CD133 as a reliable positive marker of human CB-derived CD34^– SCID-repopulating cells and succeeded in highly purifying primitive human CD34^– hematopoietic stem cells. [Leukemia] Abstract

Lamins Regulate Cell Trafficking and Lineage Maturation of Adult Human Hematopoietic Cells
Researchers hypothesized that cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and lamin levels directly modulate hematopoietic programs. [Proc Natl Acad Sci USA] Abstract

Human ProT-Cells Generated In Vitro Facilitate Hematopoietic Stem Cell-Derived T-Lymphopoiesis In Vivo and Restore Thymic Architecture
Researchers addressed whether in vitro-derived human progenitor T-cells (proT) could not only represent a source of thymus-seeding progenitors but also be able to influence the recovery of the thymic microenvironment. [Blood] Abstract

The Small Molecule Me6TREN Mobilizes Hematopoietic Stem/Progenitor Cells by Activating MMP-9 Expression and Disrupting SDF-1/CXCR4 Axis
Investigators report that the molecule Me6TREN (Me6) can induce rapid mobilization of hematopoietic progenitor cells, and that Me6 exhibits more significant effects than G-CSF or AMD3100. [Blood] Abstract

Stress Hematopoiesis Is Regulated by the Krüppel-Like Transcription Factor ZBP-89
Researchers showed that conditional deletion of ZBP-89 in adult mouse hematopoietic stem/progenitor cells causes anemia and thrombocytopenia that are transient in the steady state, but readily uncovered following chemically induced erythro/megakaryopoietic stress. [Stem Cells] Abstract

Exonuclease 1 Is a Critical Mediator of Survival during DNA Double Strand Break Repair in Non-Quiescent Hematopoietic Stem and Progenitor Cells
Scientists used cultured Exo1^mut fibroblasts and bone marrow to demonstrate that loss of Exo1 function results in defective homologous recombination (HR) in cycling cells. Conversely in Exo1^mut mice HR is not required for maintenance of quiescent hematopoietic stem cells (HSCs) at steady state, confirming the steady state HSC reliance on non-homologous end joining. [Stem Cells] Abstract

Resistance of Hematopoietic Progenitors to Fas-Mediated Apoptosis Is Actively Sustained by NFκB with a Characteristic Transcriptional Signature
Researchers evaluated the molecular mechanisms of progenitor resistance to apoptosis triggered by Fas cross-linking. CD34+ and lineage-negative progenitors survive short-term ex vivo incubation and are not induced into apoptosis by Fas cross-linking. [Stem Cells Dev] Abstract

Autocrine GM-CSF Transcription in the Leukemic Progenitor Cell Line KG1a Is Mediated by the Transcription Factor ETS1 and Is Negatively Regulated through SECTM1 Mediated Ligation of CD7
Secreted and transmembrane protein 1 (SECTM1) is expressed in Human Bone Marrow Endothelial Cells and its expression can be upregulated by IFN-γ. KG1a cells demonstrated high expression levels of CD7 and ETS-1 allowing a constitutative signaling through the PI3K/Atk pathway to promote GM-CSF expression, while KG1 cells with low expression of CD7 and ETS-1 showed low GM-CSF expression. [Biochim Biophys Acta] Abstract

CLINICAL RESEARCH

Allogeneic Stem Cell Transplantation for Advanced Cutaneous T-Cell Lymphomas: A Study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas
Researchers performed a multicenter retrospective analysis of 37 cases of advanced-stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 transformed mycosis fungoides. [Haematologica] Abstract

High Incidence of Chronic Graft-Versus-Host Disease after Myeloablative Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia in Sweden: Graft-Versus-Leukemia Effect Protects against Relapse
Between 1994 and 2007, 48 adults underwent allo-stem cell transplantation for poor-risk chronic lymphocytic leukemia in Sweden. The cumulative incidence of acute graft-versus-host disease grades II-IV was 30%. The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. [Med Oncol] Abstract

Regulation of Hematopoietic Stem Cells by Bone Marrow Stromal Cells
The authors review the complex and diverse stromal cell populations that reside in the bone marrow and examine their contribution to hematopoietic stem cells maintenance. [Trends Immunol] Abstract | Full Article

Leukemia Stem Cells in Personalized Medicine
The authors highlight recent advances in the understanding of leukemic stem cell biology and their potential for translation into clinically relevant therapeutics. [Stem Cells] Abstract | Full Article

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Polaris Group Announces Treatment of First Patient in Phase II Study of ADI-PEG 20 in Acute Myeloid Leukemia
Polaris Group announced that the first patient has been dosed in its Phase II trial of ADI-PEG 20, arginine deiminase formulated with polyethylene glycol, for the treatment of Relapsed/Refractory Acute Myeloid Leukemia. [PR Newswire Association LLC] Press Release

STEMCELL Technologies Receives Government of Canada Support to Develop New Cell Isolation Technology that Will Enable Advancements in the Study of the Immune Response to HIV and the Development of HIV Vaccines
STEMCELL Technologies announced that the National Research Council of Canada Industrial Research Assistance Program will provide up to $1.5 million in financial support for the development of cell isolation technology that will further basic and translational HIV research as well as broader research in infectious disease. [STEMCELL Technologies Inc.] Press Release

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Director of Sponsored Programs (Wake Forest Institute for Regenerative Medicine)

Adult Stem Cell Transplant Physician (John Theurer Cancer Center)

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)

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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