Hematopoiesis News 10.02 January 22, 2019 | |
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TOP STORYConditional deletion of stem cell factor (SCF) from leptin receptor+ (LepR+) cells depleted common myeloid progenitors, common lymphoid progenitors, granulocyte-macrophage progenitors, megakaryocyte-erythrocyte progenitors, pre-megakaryocyte-erythrocyte progenitors, and colony-forming units-erythroid, as well as myeloid and erythroid blood cells. This was not caused by HSC depletion, as many other restricted progenitors were unaffected. [Cell Stem Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists report a myelodysplastic syndromes (MDS) patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that provided efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts reproduced patients’ dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. [Nat Commun] Full Article Mechanisms of Thrombocytopenia in Platelet-Type Von Willebrand Disease Platelet-type von Willebrand disease megakaryocytes bound von Willebrand factor at an early differentiation stage and generated proplatelets with a decreased number of enlarged tips as compared with control megakaryocytes. Moreover, they formed proplatelets upon contact with collagen, differently from normal megakaryocytes. [Haematologica] Abstract | Full Article The ALK Inhibitor AZD3463 Effectively Inhibits Growth of Sorafenib-Resistant Acute Myeloid Leukemia Researchers used cell lines derived from the AML cell line MOLM-13 that were either sensitive or resistant to the multikinase inhibitor sorafenib. The resistant cell line was generated by long-term treatment of MOLM-13 cells with sorafenib. Sorafenib-resistant cells acquired a secondary mutation in the kinase domain of FLT3 and also displayed upregulation of the PI3K/mTOR pathway. [Blood Cancer J] Full Article CCI-006 inhibited mitochondrial respiration and induced mitochondrial membrane depolarization and apoptosis in a subset of mixed lineage leukemia (MLL)-rearranged leukemia cell lines within a few hours of treatment. The unresponsive MLL-rearranged leukemia cells did not undergo mitochondrial membrane depolarization or apoptosis despite a similar attenuation of mitochondrial respiration by the compound. [Oncogene] Full Article Investigators demonstrated that memantine inhibited Kv1.3 channels of acute leukemia cells and in combination with cytarabine potentiates cell death of acute lymphoid and myeloid leukemia cell lines as well as primary leukemic blasts from acute leukemia patients. Memantine co-application fostered concurrent inhibition of AKT, S6 and ERK1/2 and reinforced nuclear down-regulation of MYC, a common target of AKT and ERK1/2 signaling. [Cell Commun Signal] Full Article Rescue of Hematopoietic Stem/Progenitor Cells Formation in plcg1 Zebrafish Mutant The authors focused on hematopoietic stem/progenitor cells (HSPC) development in phospholipase C gamma 1 (plcg1−/−) mutants and showed that ginger/10-gingerol could rescue the expression of arterial and HSPC markers in the hemogenic endothelium and caudal hematopoietic tissue in plcg1−/− mutant embryos. [Sci Rep] Full Article Researchers analyzed the role of sphingolipid signaling in erythropoiesis and demonstrated that sphingosine kinase activity promoted terminal erythroid differentiation by regulating the expression of key mitophagy genes Pink1 and Bnip3l/Nix. Sphk1 inhibition also disrupted Pink1-p62 mediated mitochondria clearance in late erythroblasts. [Exp Hematol] Abstract TAL1 directly activated the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation. Scientists found that FUBP1 expression was required for efficient erythropoiesis, as FUBP1-deficient progenitor cells were limited in their potential of erythroid differentiation. [PLoS One] Full Article CLINICAL RESEARCHInvestigators treated three adults and six children with absent hemoglobin production or severe reduced mutations in a Phase I/II trial with an intrabone administration of HSCs transduced with the lentiviral vector GLOBE. Rapid hematopoietic recovery with polyclonal multilineage engraftment of vector-marked cells was achieved, with a median of 37.5% in hematopoietic progenitors and a vector copy number per cell of 0.58 in erythroid precursors at one-year, in absence of clonal dominance. [Nat Med] Abstract | Press Release Estimated eight-year overall survival was comparable between the immunosuppressive therapy (IST) and haploidentical donors (HID) HSC transplantation (HSCT) groups, but failure free survival (FFS) was significantly lower in IST group than HID HSCT group. Furthermore, a significant improvement in FFS was observed with HSCT over IST in patients under 40 years old. [Bone Marrow Transplant] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSThe authors highlight recent advances in the application of induced pluripotent stem (iPS) cells for disease modeling of bone marrow failure syndromes and discuss the discoveries of these studies that provide new insights in the pathophysiology of these conditions. [Exp Hematol] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSGamida Cell and Be the Match BioTherapies® Announce Strategic Collaboration The collaboration supports NiCord®, Gamida Cell’s investigational cell therapy, which has the potential to serve as a universal bone marrow donor source for patients with hematologic malignancies, or blood cancers, and bone marrow failure disorders requiring bone marrow transplantation. [Gamida Cell Ltd.] Press Release Nexus Pharmaceuticals Announces FDA Approval of Busulfan Injection Nexus Pharmaceuticals Inc. announced the FDA approval of Busulfan Injection, the company’s AP-rated therapeutic equivalent for Busulfex® 60 mg/10 mL. Busulfan is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. [Nexus Pharmaceuticals Inc.] Press Release Genmab A/S announced that its licensing partner, Janssen Biotech, Inc., has submitted the first part of a regulatory submission to the FDA for a label expansion to include the use of daratumumab in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant. [Genmab A/S] Press Release TG Therapeutics, Inc. announced that the FDA has granted Breakthrough Therapy Designation for umbralisib for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 regimen. There are currently no fully approved agents for MZL. [TG Therapeutics, Inc.] Press Release | |
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POLICY NEWSScientist Behind CRISPR Twins Sharply Criticized in Government Probe, Loses Job He Jiankui, the Chinese researcher who claimed to have edited the genomes of twin baby girls in a heritable way—and earned widespread condemnation for conducting a risky procedure with little potential benefit—deliberately sidestepped regulations, dodged oversight, and used fake ethical review documents in hopes of gaining “personal fame” for a worldwide first, according to preliminary results from a Chinese governmental investigation. [ScienceInsider] Editorial How Estonia Blazed a Trail in Science Since it joined the European Union (EU) in 2004, Estonia has spent more than €1 billion in EU funds on modernizing its research base. It now boasts strengths in numerous fields, including ecology, molecular biology and genetics, and has built up extensive international research networks. [Nature News] Editorial
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EVENTSNEW 2nd London Stem Cell Network Symposium Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Investigator Positions – Hematologic Malignancies (University of Alabama Birmingham) NEW Postdoctoral Associate – T-ALL Research (University of New Mexico) NEW Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University) Postdoctoral Research Scholar – Hematologic Malignancies (Washington University School of Medicine) Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine) Research Fellow – Myeloid Leukemia (University College of London) Postdoctoral Scholar – Cancer Development (University of Southern California) 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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