Volume 6.11 | Mar 24

Hematopoiesis News 6.11 March 24, 2015
Hematopoiesis News
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Even at a Molecular Level, Taking It Slow Helps Us Cope with Stress
Scientists identified a new molecular pathway critical to aging, and confirmed that the process can be manipulated to help make old blood like new again. They found that blood stem cells’ ability to repair damage caused by inappropriate protein folding in the mitochondria is critical to their survival and regenerative capacity. [Press release from University of California, Berkeley discussing online publication in Science]
Press Release | Abstract
March Magnet Maddness: Free EasySep™ Magnet with Purchase of Cell Isolation Reagents
PUBLICATIONS (Ranked by impact factor of the journal)
IP3 3-Kinase B Controls Hematopoietic Stem Cell Homeostasis and Prevents Lethal Hematopoietic Failure in Mice
Investigators identified inositoltrisphosphate (IP3) 3-kinase B (Itpkb) as an essential regulator of hematopoietic stem cell (HSC) homeostasis. Young Itpkb-/- mice accumulated phenotypic HSC which were less quiescent and proliferated more than wildtype controls. [Blood] Abstract | Press Release

Autophagy Is Required for Stem Cell Mobilization by G-CSF
Scientists observed that granulocyte-colony stimulating factor (G-CSF) activates autophagy in neutrophils and hematopoietic stem cell from both mouse and human donors. [Blood] Abstract

Microenvironmental Remodeling as a Parameter and Prognostic Factor of Heterogeneous Leukemogenesis in Acute Myeloid Leukemia
Researchers assessed the bone marrow microenvironment of acute myeloid leukemia patients and demonstrated that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells. [Cancer Res] Abstract

IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia
To determine whether mutant IDH enzymes are valid targets for cancer therapy, scientists created a mouse model of acute myeloid leukemia (AML) in which mice were transplanted with nucleophosmin1 (NPM1)+/- hematopoietic stem/progenitor cells co-transduced with four mutant genes which often occur simultaneously in human AML patients. [Cancer Res] Abstract

Cyclin A1 Regulates the Interactions between Mouse Hematopoietic Stem and Progenitor Cells and Their Niches
Investigators showed that the cell cycle regulator cyclin A1 in association with vascular endothelial growth factor receptor 1, is required for hematopoietic stem/progenitor cells and their niches to maintain their function and proper interaction. [Cell Cycle] Abstract

Standard Sub-Thermoneutral Caging Temperature Influences Radiosensitivity of Hematopoietic Stem and Progenitor Cells
Researchers report that the mild, but chronic cold-stress endured by mice housed under laboratory conditions exerts a protective effect on hematopoietic stem and progenitor cells after both non-lethal and lethal doses of total body irradiation. [PLoS One] Full Article

MicroRNA-223 Regulates Granulopoiesis but Is Not Required for HSC Maintenance in Mice
The authors characterized hematopoietic stem cell (HSC) function and myeloid differentiation in miR223 deficient mice. They showed that miR223 loss results in a modest expansion of myeloid progenitors, but is not sufficient to induce a myeloproliferative disorder. [PLoS One] Full Article


Phase III Trial of Bortezomib, Cyclophosphamide, Dexamethasone (VCD) versus Bortezomib, Doxorubicin, Dexamethasone (PAd) in Newly-Diagnosed Myeloma
Investigators aimed at demonstrating non-inferiority of VCD compared to PAd induction therapy with respect to very good partial response rates or better in 504 newly diagnosed, transplant-eligible multiple myeloma patients. [Leukemia] Abstract

Allogeneic Transplantation with Myeloablative FluBu4 Conditioning Improves Survival Compared to Reduced Intensity FluBu2 Conditioning for Acute Myeloid Leukemia in Remission
Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, researchers reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. [Ann Hematol] Abstract

Allogeneic Stem Cell Transplantation Using Lymphoablative Rather than Myeloablative Conditioning Regimen for Relapsed or Refractory Lymphomas
Investigators treated 28 relapsed or refractory non-Hodgkin lymphomas with allogeneic hematopoietic stem cell transplantation. All were pre-conditioned with fludarabine and melphalan; 25 were additionally treated with total body irradiation. [Hematol Oncol] Abstract

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In Situ Hematopoiesis: A Regulator of TH2 Cytokine-Mediated Immunity and Inflammation at Mucosal Surfaces
The authors highlight the differences between homeostatic hematopoiesis, which occurs in the bone marrow, and in situ hematopoiesis, which occurs at mucosal surfaces. They also highlight factors produced at local sites of inflammation that regulate hematopoietic progenitor cell responses and the development of TH2 cytokine-mediated inflammation. [Mucosal Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.
Kamada Awarded European Orphan Drug Designation for Its Alpha-1 Antitrypsin to Treat Graft-versus-Host Disease
Kamada Ltd. announces that the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, has designated the company’s proprietary human intrevenous alpha-1 antitrypsin as an orphan medicinal product to treat graft-versus-host disease. [Kamada Ltd.] Press Release

MEI Pharma Announces Top-Line Data from Randomized Phase II Clinical Study of Pracinostat in Front-Line Myelodysplastic Syndrome
MEI Pharma, Inc. announced top-line data from a randomized Phase II clinical study of its investigational drug candidate Pracinostat in combination with azacitidine in patients with previously untreated intermediate-2 or high-risk myelodysplastic syndrome. According to the top-line data, the combination of Pracinostat and azacitidine showed no difference in the rate of complete remission, the study’s primary endpoint, compared to azacitidine alone. [MEI Pharma, Inc.] Press Release

Cellerant Announces Dosing of First Patient in Randomized Phase II Clinical Trial of CLT-008 in Acute Myeloid Leukemia Patients
Cellerant Therapeutics Inc. announced that patient dosing has commenced in its multi-center, open-label, randomized controlled Phase II clinical trial of CLT-008, a first-in-class, allogeneic, cellular therapy, in de novo acute myeloid leukemia patients receiving induction chemotherapy. [Cellerant Therapeutics Inc.] Press Release

City of Hope Launches Stem Cell Therapy Clinic to Fight Incurable Disease in New Ways
The City of Hope officially opened the Alpha Clinic for Cell Therapy and Innovation for patients battling cancer and other life-threatening diseases. The Alpha Clinic is funded by an $8 million, five-year grant from the California Institute for Regenerative Medicine that will be supplemented by matching funds from City of Hope. [City of Hope] Press Release

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Therapeutic Goods Administration (Australia)
NEW Else Kröner-­Fresenius (EKF) Symposium on Adult Stem Cells in Aging, Diseases and Cancer
May 31-June 3, 2015
Erice, Italy

Visit our events page to see a complete list of events in the hematopoiesis community.
NEW Postdoctoral Research Fellow – Hematopoietic Stem Cell Biology (University of Leuven)

Research Technologist – Hematopoietic Product Development (STEMCELL Technologies Inc.)

Principal Scientist – Hematopoietic Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Manufacturing Manager – Cell Therapy (Opexa Therapeutics)

Research Scientist – Cell Signaling in Normal and Leukemic Hematopoietic Stem and Progenitor Cells (Indiana University)

Postdoctoral Position – Drug Development for Anemia (Lund University)

Postdoctoral Position – Pediatric Hematology and Oncology (University Medical Center of Freiburg)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Director – Vector Production (Sangamo BioSciences, Inc.)

Postdoctoral Position – Genetic Engineering and Transplantation of Hematopoietic Stem Cells (University of California – San Francisco)

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