Hematopoiesis News 10.00 January 8, 2019 | |
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TOP STORYResearchers demonstrated that SRPK1 inhibition led to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24. [Nat Commun] Full Article | Press Release | Editorial | |
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PUBLICATIONS(Ranked by impact factor of the journal)Murine Hematopoietic Stem Cell Activity Is Derived from Pre-Circulation Embryos but Not Yolk Sacs Scientists report robust, multi-lineage and serially transplantable definitive HSC (dHSC) activity from cultured 2-7 somite pair (sp) murine embryonic explants (Em-Ex). dHSC were undetectable in 2-7sp yolk sac explants. Additionally, the engraftment from Em-Ex was confined to an emerging CD31+CD45+c-Kit+CD41− population. [Nat Commun] Full Article Dasatinib and Navitoclax Act Synergistically to Target NUP98–NSD1+/FLT3-ITD+ Acute Myeloid Leukemia Researchers found that mouse hematopoietic progenitors co-expressing NUP98-NSD1 and FLT3-ITD had significantly increased sensitivity to FLT3 and MEK-inhibitors compared to cells expressing either aberration alone. [Leukemia] Abstract JMJD1C-Mediated Metabolic Dysregulation Contributes to HOXA9-Dependent Leukemogenesis Targeting JMJD1C-mediated metabolism via pharmacologic inhibition of glycolysis and oxidative phosphorylation led to ATP depletion, induced necrosis/apoptosis and decreased tumor growth in vivo in leukemias co-expressing JMJD1C and homeobox A9 (HOXA9). The anti-metabolic therapy effectively diminished acute myeloid leukemia (AML) stem/progenitor cells and reduced tumor burden in a primary AML patient-derived xenograft. [Leukemia] Abstract Clonal-Level Lineage Commitment Pathways of Hematopoietic Stem Cells In Vivo Under homeostasis, all donor-derived HSC clones regenerated blood homogeneously throughout all measured stages and lineages of hematopoiesis. In contrast, after the hematopoietic system had been perturbed by irradiation or by an antagonistic anti-ckit antibody, only a small fraction of donor-derived HSC clones differentiated. [Proc Natl Acad Sci USA] Abstract The authors found a functionally important AML1-ETO-containing transcription factor complex (AETFC) heterogeneity defined by the three E proteins: while HEB and E2A facilitated leukemogenesis, E2-2 functioned as a negative regulator. [Proc Natl Acad Sci USA] Abstract | Press Release An analysis of near-full-length genomes isolated from hematopoietic stem and progenitor cells (HSPCs) provided evidence that HSPCs harbor functional HIV proviral genomes that often match residual plasma virus. [Cell Rep] Full Article Investigators developed TALENs targeting the homologous HBG promoters to de-repress fetal hemoglobin. Erythroid differentiation of edited cells revealed a 4.6-fold increase in γ-hemoglobin expression as detected by HPLC. Assessment of TALEN edited CD34+ cells in vivo in a humanized mouse model demonstrated sustained presence of indels in hematopoietic cells up to 24 weeks. [Mol Ther Methods Clin Dev] Abstract | Full Article | Graphical Abstract CLINICAL RESEARCHPatients were given intravenous sintilimab until progression, death, unacceptable toxicity, or withdrawal of consent. The primary outcome was the proportion of patients in the full analysis set who had an objective response, as assessed by an independent radiological review committee, by 24 weeks after enrollment of the last patient. [Lancet Haematol] Abstract | Press Release Researchers performed a large registry study that included 535 patients with therapy-related acute myeloid leukemia and prior solid tumor who underwent first myeloablative or reduced-intensity conditioning allogeneic hematopoietic cell transplantation from 2000-2016. LFS and OS were superior in patients receiving ablative regimens due to a decrease in relapse. [Am J Hematol] Abstract Patients receiving allogenic HSC transplantation (alloHSCT) obtained improved overall survival (OS) than patients who treated with chemotherapy. With alloHSCT, the outcome of patients who reached negative minimal residual disease after two cycles of consolidation could be further improved with an increased OS of 66% and relapse-free survival of 61%. [Ann Hematol] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSHematopoiesis in the Era of Advanced Single-Cell Technologies The authors review recent relevant work from the hematopoietic system and discuss how to interpret and integrate data obtained with different technologies. [Nat Cell Biol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSmiRagen Therapeutics, Inc. announced that it will present new data from its Phase I trial of cobomarsen in HTLV-1 associated adult T-cell leukemia/lymphoma as well as its Phase I trial of cobomarsen in patients with mycosis fungoides, the most common form of cutaneous T-cell. [Press release from miRagen Therapeutics, Inc. discussing research to be presented at the 11th Annual T-Cell Lymphoma Forum, La Jolla] Press Release | |
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INDUSTRY NEWSTakeda Pharmaceutical Company Limited announced new research collaborations in immuno-oncology, an area of key strategic focus for the company. Takeda’s diversification into next-generation cell therapy builds directly on its three strategic pillars in oncology: hematologic malignancies, lung cancer and immuno-oncology. [Takeda Pharmaceutical Company Limited] Press Release Auron Therapeutics and Elucidata Corporation announced a scientific collaboration using Elucidata’s AI-based target discovery platform to identify and validate targets for differentiation-based therapy for Acute Myeloid Leukemia and eight other oncology indications. [Auron Therapeutics (Business Wire, Inc.)] Press Release Ayala Pharmaceuticals, Inc. announced that it entered into an option to license agreement with Novartis for its investigational agent AL102 in multiple myeloma. [Ayala Pharmaceuticals, Inc.] Press Release Bristol-Myers Squibb Company announced the FDA has expanded the indication for Sprycel® tablets to include the treatment of pediatric patients one year of age and older with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia in combination with chemotherapy. [Bristol-Myers Squibb Company] Press Release Innovent Biologics, Inc. and Eli Lilly and Company jointly announce that the co-developed Tyvyt® has been granted approval for market authorization by the National Medical Products Administration of China (NMPA) for the treatment of patients with classical Hodgkin’s lymphoma that has relapsed or refractory after two or more lines of systemic chemotherapy. [Innovent Biologics, Inc.] Press Release Rafael Pharmaceuticals, Inc. announced the initiation of patient enrollment for a Phase II clinical trial of CPI-613 for patients with relapsed or refractory Burkitt Lymphoma/Leukemia. In June 2018, CPI-613 received orphan drug designation for treatment of Burkitt Lymphoma from the US FDA. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release Sunesis Pharmaceuticals, Inc. announced that the company has opened the 100 mg cohort in the Phase Ib/II trial of its non-covalent BTK inhibitor vecabrutinib in adults with relapsed/refractory chronic lymphocytic leukemia (CLL) and other B-cell malignancies. [Sunesis Pharmaceuticals, Inc.] Press Release Cellectar Provides Update on Phase I Trial of CLR 131 in Relapsed/Refractory Multiple Myeloma Cellectar Biosciences announced median overall survival in cohorts 1-4 of the company’s ongoing Phase I clinical trial evaluating CLR 131 for the treatment of relapsed/refractory multiple myeloma. [Cellectar Biosciences] Press Release Janssen Announces European Commission Approval of Darzalex®▼ (Daratumumab) Split Dosing Regimen The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the European Commission has granted marketing authorization to provide healthcare professionals with the option to split the first infusion of Darzalex® over two consecutive days. [Janssen Global Services, LLC] Press Release Celyad announced that it is accelerating its clinical development strategy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and provided updates on clinical candidates CYAD-01 and CYAD-101 with key upcoming milestones for 2019. [Celyad] Press Release SELLAS Life Sciences Provides Update on Late-Stage Immunotherapy Clinical Development Pipeline SELLAS Life Sciences Group, Inc. provided a corporate update on the company’s clinical development of galinpepimut-S and nelipepimut-S, which are both in late-stage development. [SELLAS] Press Release Karyopharm Therapeutics Inc. announced that it has submitted a Marketing Authorization Application to the European Medicines Agency for selinexor, the company’s first-in-class, oral selective inhibitor of nuclear export compound. [Karyopharm Therapeutics Inc.] Press Release CHLA Scientist Awarded $1.2M to Study Drug Resistance in Leukemia Investigator Yong-Mi Kim works to uncover how the body shields leukemia cells from treatment. Her lab was the first to discover that one integrin, integrin alpha 4, anchors leukemia cells in the bone marrow, allowing them to become resistant to treatment. [Children’s Hospital Los Angeles] Press Release | |
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POLICY NEWSU.S. Government Shutdown Starts to Take a Bite Out of Science The shutdown is creating chaos for university researchers, private contractors, and others who collaborate with idled federal scientists, or depend on affected agencies for funding, facilities, and data. Besides doing lasting damage to some research projects, the standstill is threatening livelihoods. [ScienceInsider] Editorial Swiss Researchers Struggle to Get Animal Experiments Approved Scientists say that increasingly rigorous licensing procedures have complicated research efforts—and in some cases, stopped experiments completely. [The Scientist] Editorial How Much Do Graduate Students Benefit From Studying Abroad? The National Science Foundation is rethinking how to provide U.S. graduate students with a chance to do science in another country. It also wants to know whether its current foreign travel programs are working. [ScienceInsider] Editorial
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EVENTSNEW 15th Annual Stem Cell Symposium: Stem Cells B2B – Bench to Bedside Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine) NEW Research Fellow – Myeloid Leukemia (University College of London) Research Technologist – Hematopoietic (STEMCELL Technologies Inc.) Postdoctoral Scholar – Cancer Development (University of Southern California) Research Officer – Hematopoietic Stem Cells (The University of Queensland) Postdoctoral Position – Regenerative Medicine, Stem Cells and Bioengineering (Igenomix Foundation) Staff Scientist – Hematology (St. Jude Children’s Research Hospital) Assistant Project Scientist – Hematology and Oncology (University of California, Davis) Research Scientist – Hematological Malignancies (MD Anderson Cancer Center) Faculty Positions – Hematology and Oncology (UC Davis) 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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