Hematopoiesis News Volume 2.17 | May 3 2011

Mystery Solved: How Sickle Hemoglobin Protects Against Malaria
In a study that challenges currently held views, researchers unravel the molecular mechanism whereby sickle cell hemoglobin confers a survival advantage against malaria, the disease caused by Plasmodium infection. [Press release from the Instituto Gulbenkian de Ciência discussing online prepublication in Cell]

Low Vitamin D in Kids May Play a Role in Anemia
Pediatricians have discovered a link between low levels of vitamin D and anemia in children. [Press release from Johns Hopkins Children’s Center discussing research presented at the Annual Meeting of the Pediatric Academic Societies]

LABORATORY RESEARCH

Sickle Hemoglobin Confers Tolerance to Plasmodium Infection
Findings provide insight into molecular mechanisms via which sickle hemoglobin confers host tolerance to severe forms of malaria. [Cell]

Pomalidomide Augments Fetal Hemoglobin Production without the Myelosuppressive Effects of Hydroxyurea in Transgenic Sickle Cell Mice
Researchers investigated the effects of pomalidomide on erythropoiesis and hemoglobin synthesis in a transgenic mouse model of sickle cell disease. [Blood]

ERG Promotes T-Acute Lymphoblastic Leukemia and Is Transcriptionally Regulated in Leukemic Cells by a Stem Cell Enhancer
Investigators demonstrate that transgenic expression of ERG causes T-acute lymphoblastic leukemia (T-ALL) in mice and that its knockdown reduces the proliferation of human MOLT4 T-ALL cells. [Blood]

Depletion of CD25⁺ T Cells from Hematopoietic Stem Cell Grafts Increases Post-Transplant Vaccine-Induced Immunity to Neuroblastoma
Because increased percentages of Treg cells are seen in hematopoietic stem cell transplant recipients, scientists hypothesized that the inhibitory effect of CD4 T cells is primarily due to the presence of expanded Treg cells. [Blood]

Dexamethasone and Lenalidomide Have Distinct Functional Effects on Erythropoiesis
Researchers explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. [Blood]

Bromodomain Protein Brd3 Associates with Acetylated GATA1 to Promote Its Chromatin Occupancy at Erythroid Target Genes
Investigators show that the BET family protein Brd3 binds via its first bromodomain to GATA1 in an acetylation-dependent manner in vitro and in vivo. [Proc Natl Acad Sci U S A]

Bmi1 Is Essential for Leukemic Reprogramming of Myeloid Progenitor Cells
Findings indicate that Bmi1 is essential for the faithful reprogramming of myeloid progenitors into leukemic stem cells (LSCs) and unveil that leukemic fusion genes require polycomb group proteins exerting an effect in concert to establish LSC-specific transcriptional profiles, which confer full leukemogenic activity on LSCs. [Leukemia]

Tensin2 Is a Novel Mediator in Thrombopoietin-Induced Cellular Proliferation by Promoting Akt Signaling
Using an unbiased approach with peptide microarrays that contained virtually every Src Homology 2 and Phosphotyrosine Binding Domains in the human genome, scientists discovered a previously unreported interaction between c-Mpl at phospho-Tyrosine631 and Tensin2, a protein for which limited information is available. [Cell Cycle]

CLINICAL RESEARCH

Treatment-Related Risk Factors for Transformation to Acute Myeloid Leukemia and Myelodysplastic Syndromes in Myeloproliferative Neoplasms
Using population-based data from Sweden, researchers assessed the role of myeloproliferative neoplasm treatment and subsequent acute myeloid leukemia/myelodysplastic syndrome risk with special focus on the leukemogenic potential of hydroxyurea. [J Clin Oncol]

Prognostic Significance of Immunohistochemical Biomarkers in Diffuse Large B-Cell Lymphoma: A Study from the Lunenburg Lymphoma Biomarker Consortium
The Lunenburg Lymphoma Biomarker Consortium evaluated the prognostic value of immunohistochemical biomarkers in a large series of patients with diffuse large B-cell lymphoma. [Blood]

Alternative Donor Transplantation: Results of Parallel Phase II Trials Using HLA-Mismatched Related Bone Marrow or Unrelated Umbilical Cord Blood Grafts
The Blood and Marrow Transplant Clinical Trials Network conducted two parallel multi-center phase II trials for individuals with leukemia or lymphoma and no suitable related donor. [Blood]

Prognostic Impact of FLT3-ITD Load in NPM1 Mutated Acute Myeloid Leukemia
To clarify whether FLT3-ITD load as expressed as FLT3-ITD /wildtype (wt) ratio is also relevant in patients with NPM1 mutated AML, scientists assessed the FLT3-ITD mutation status and FLT3-ITD /wt ratio by fragment analysis in 638 NPM1mut AML (339 females; 299 males; 17.8–88.0 years), and analyzed its prognostic relevance in 355 patients. [Leukemia]

Long-Acting Erythropoiesis Stimulating Agent,“Mircera® Injection Syringe,” Approved in Japan
Chugai Pharmaceutical Co., Ltd. announced that it has obtained manufacturing and marketing approval from the Ministry of Health, Labour and Welfare on April 22, 2011, for a long-acting erythropoiesis stimulating agent [brand name: Mircera® Injection Syringe], with indication for use in the treatment of renal anemia. [Chugai Pharmaceutical Co., Ltd. Press Release]

Seattle Genetics Announces FDA Accepts Brentuximab Vedotin BLAs for Filing and Grants Priority Review for Relapsed or Refractory Hodgkin Lymphoma and Systemic ALCL
Seattle Genetics, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted for filing two Biologics License Applications (BLAs) for brentuximab vedotin, including one for the treatment of patients with relapsed or refractory Hodgkin lymphoma and one for the treatment of patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). [Seattle Genetics, Inc. Press Release]

Rockwell Medical Begins Second Phase III Clinical Trial for Treatment of Iron Deficiency in Dialysis Patients
Rockwell Medical announced that it has initiated enrollment in its second pivotal Phase III clinical study called CRUISE-2, designed to treat iron deficiency anemia in hemodialysis dependent-chronic kidney disease patients receiving erythropoietin. [Rockwell Medical Press Release]

Sangart Announces Closing of $50 Million Series G Financing
Sangart, Inc., announced that it recently received more than $50 million in new equity funding from existing investors, led by Leucadia National Corporation. [Sangart, Inc. Press Release]

Pharmacyclics Achieves $7 Million Development Milestone for HDAC Inhibitor, PCI-24781/S 78454 with Servier
Pharmacyclics, Inc. announced that it has received a $7 million milestone payment for its histone deacetylase (HDAC) inhibitor, PCI-24781/S 78454 from Les Laboratoires Servier based on an ex-US collaboration agreement signed in April of 2009. [Pharmacyclis, Inc. Press Release]

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)
 
European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW CIRM/Regenerative Medicine Consortium – Imaging Technology for Cellular Therapies
May 26, 2011
Webinar

NEW Keystone Symposia: Changing Landscape of the Cancer Genome
June 20-25, 2011
Boston, United States

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