Hematopoiesis News 10.20 May 28, 2019 | |
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TOP STORYTargeted Homology-Directed Repair in Blood Stem and Progenitor Cells with CRISPR Nanoformulations Scientists developed a CRISPR nanoformulation based on colloidal gold nanoparticles with a unique loading design capable of cellular entry without the need for electroporation or viruses. This highly monodispersed nanoformulation avoided lysosomal entrapment and localized to the nucleus in primary human blood progenitors without toxicity. [Nat Mater] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia Researchers used single-cell RNA sequencing to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy. They identified seventeen stromal subsets expressing distinct hematopoietic regulatory genes spanning new fibroblastic and osteoblastic subpopulations including distinct osteoblast differentiation trajectories. [Cell] Abstract | Press Release | Graphical Abstract The AAA+ ATPase RUVBL2 Is Essential for the Oncogenic Function of c-MYB in Acute Myeloid Leukemia The authors showed that transcriptional repression of myeloid differentiation associated c-MYB target genes in AML was enforced by the AAA+ ATPase RUVBL2. Silencing RUVBL2 expression resulted in increased binding of c-MYB to these loci and their transcriptional activation. RUVBL2 inhibition resulted in AML cell apoptosis and severely impaired disease progression of established AML in engrafted mice. [Leukemia] Abstract Disruption of the Myc-PDE4B Regulatory Circuitry Impairs B-Cell Lymphoma Survival Investigators demonstrated the presence of a Myc-phosphodiesterase 4B (PDE4B) feed-forward loop, in which Myc and PDE4B mutually reinforced the expression of each other. The combined targeting of Myc and PDE4 synergistically prevented the proliferation and survival of B lymphoma cells in vitro and in a mouse xenograft model. [Leukemia] Abstract Scientists determined the anti-leukemia efficacy of concomitant targeting of BCL2 and MAPK pathways by venetoclax and MEK1/2 inhibitor cobimetinib respectively. The combination demonstrated synergy in seven of eleven acute myeloid leukemia cell lines, including those resistant to single agents, and showed growth-inhibitory activity in over 60% of primary patient samples with diverse genetic alterations. [Haematologica] Abstract High Activation of STAT5A Drives Peripheral T-Cell Lymphoma and Leukemia Given the shortage of models for peripheral T-cell lymphoma, researchers mimicked graded STAT5A or STAT5B activity by expressing hyperactive Stat5a or STAT5B variants at low or high levels in the hematopoietic system of transgenic mice. Only high activity levels developed a lethal disease resembling human peripheral T-cell lymphoma. [Haematologica] Abstract Investigators compared the activity of ZFNs and CRISPR/Cas9 for editing and homologous donor templates delivered as single-stranded oligodeoxynucleotides, adeno-associated virus serotype 6, integrase-deficient lentiviral vectors and adenovirus 5/35 serotype to transvert the base-pair responsible for sickle cell disease in HBB in primary human CD34+ hematopoietic stem and progenitor cells. [Mol Ther] Abstract | Graphical Abstract The authors proved that BCR-ABL1 tyrosine kinase-dependent hyper-activation of aurora kinase A-Polo-like kinase 1-FOXM1 axis is associated with the outcome of imatinib resistance in an experimental model and bone marrow hematopoietic cells. Notably, such a biomolecular trait was detected in the putative leukemic stem cell compartment characterized by a CD34+ phenotype. [J Exp Clin Cancer Res] Full Article CLINICAL RESEARCHAMT-060 (anti-adeno-associated virus 5 (AAV5)-human (h)FIX) was evaluated in ten adults with hemophilia B that tested negative for pre-existing AAV5 neutralizing antibodies (NABs) using a green fluorescent protein-based assay. Investigators showed that three of those ten patients tested positive for anti-AAV5 NABs using a more sensitive luciferase-based assay. However, no relationship was observed between the presence of pre-treatment anti-AAV5 NABs and the therapeutic efficacy of AMT-060. [Mol Ther Methods Clin Dev] Abstract | Full Article The Effect of Intravenous Iron on Erythropoiesis in Older People with Hip Fracture Researchers examined the impact of intravenous iron on erythropoiesis following hip fracture. The intervention group received three doses of 200 mg iron sucrose over 30 minutes on three separate days. Primary outcome was reticulocyte count at day seven after randomization. Secondary outcomes included hemoglobin concentration, complications and discharge destination. [Age Ageing] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSRole of MicroRNAs, CircRNAs and Long Noncoding RNAs in Acute Myeloid Leukemia The authors briefly describe the characteristics and molecular functions of three groups of noncoding RNAs, including long noncoding RNAs (lncRNAs), miRNAs, and circular RNAs (circRNAs), and discuss their relationships with acute myeloid leukemia in detail. [J Hematol Oncol] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSRexgenero announced that it has successfully expanded manufacturing of its lead development candidate REX-001 through a partnership with the German Red Cross Blood Donor Service in Frankfurt, Germany, signed earlier this year. [Rexgenero Ltd.] Press Release Celgene Corporation announced the FDA approved REVLIMID® in combination with a rituximab product for the treatment of adult patients with previously treated follicular lymphoma or marginal zone lymphoma following Priority Review designation. [Celgene Corporation] Press Release | |
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POLICY NEWSTaiwan Considers Double-Blind Peer Review for Grants Taiwan’s science ministry is thinking of introducing double-blind peer review to assess research-grant proposals, a trend being adopted by some journals to eliminate bias. [Nature News] Editorial Brazilian Scientists Strive to Turn Politicians into Allies Brazil’s scientists are fighting back against President Jair Bolsonaro’s plans to slash funding for research and education programs. Researchers have joined with members of Brazil’s legislature, the National Congress, to highlight the strategic role that science, technology, and education play in the country’s economic and social development. [Nature News] Editorial
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EVENTSNEW Cell Symposia: Hallmarks of Cancer Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University) Postdoctoral Scientist – Hematopoietic Stem Cell Research (DKFZ / HI-STEM) Postdoctoral Scientist – Inflammatory Stress in the Bone Marrow (DKFZ / HI-STEM) Postdoctoral Fellow – Molecular Mechanisms of Myeloma (City of Hope) Assistant Professor – Lymphoma/Myeloma Research (The University of Texas MD Anderson Cancer Center) Postdoctoral Fellows – Hematological Malignancies & Cancer Immunology (Fox Chase Cancer Center) Postdoctoral Fellowship – Myeloma Research (University of Calgary) Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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