Hematopoiesis News 10.06 February 19, 2019 | |
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TOP STORYSleep Modulates Hematopoiesis and Protects against Atherosclerosis Whereas hypocretin-null and hematopoietic hypocretin-receptor-null mice developed monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either hematopoietic CSF1 deficiency or hypocretin supplementation had reduced numbers of circulating monocytes and smaller atherosclerotic lesions. [Nature] Abstract | Press Release | Editorial | |
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PUBLICATIONS(Ranked by impact factor of the journal)Researchers used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of influencing cellular commitment to apoptosis, using sensitization to the BCL-2 inhibitor ABT-199 in BCL-2-dependent acute myeloid leukemia (AML) cell lines as a proxy for apoptotic disposition. [Cell Metab] Abstract | Graphical Abstract The authors showed that oncogenic N-RasG12D activated IRE1α-XBP1, through MEK-GSK3β, to promote HSC survival under endoplasmic reticulum stress. Inhibiting IRE1α-XBP1 abolished N-RasG12D-mediated survival under endoplasmic reticulum stress and diminished the competitive advantage of NrasG12D HSCs in transplant recipients. [Nat Cell Biol] Abstract Interferon-stimulated gene expression was upregulated in the absence of plant homeodomain finger 6 (PHF6) in hematopoietic stem and progenitor cells. The numbers of hematopoietic progenitor cells and cycling hematopoietic stem and progenitor cells were restored to normal by combined loss of PHF6 and the interferon alpha and beta receptor subunit 1. [Blood] Abstract Researchers showed that a LNK-associated lysine63– (K63-) deubiquitinating complex, BRISC attenuated HSC expansion through the control of JAK2 signaling. They pinpointed a direct interaction between the LNK SH2 domain and a phosphorylated tyrosine residue in KIAA0157, a unique and defining BRISC component. [Blood] Abstract RUNX Proteins Desensitize Multiple Myeloma to Lenalidomide via Protecting IKZFs from Degradation Interaction with runt-related transcription factor 1 (RUNX1) and RUNX3 inhibited cereblon-dependent binding, ubiquitylation, and degradation of ikaros family zinc finger protein 1 (IKZF1) and IKZF3 upon lenalidomide treatment. Inhibition of RUNXs, via genetic ablation or a small molecule, resulted in sensitization of myeloma cell lines and primary tumors to lenalidomide. [Leukemia] Full Article Scientists hypothesized that reverse signaling through programmed death-1 (PD-1) ligands may be a potential mechanism contributing to the growth and survival of Hodgkin Reed-Sternberg cells in classical Hodgkin lymphoma (HL). They showed that engagement of PD-L1 using an agonistic monoclonal antibody increased cell survival and proliferation and reduced apoptosis in HL cell lines. [Blood Cancer J] Abstract Researchers demonstrated that, among all five CBX Polycomb proteins, only CBX7 possessed the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted in increased multi-lineage long-term engraftment and myelopoiesis. [Cell Rep] Full Article | Graphical Abstract The authors developed an inhibitor, LYZ-81, which targeted ORP4L with high affinity and specificity and selectively eradicated leukemia stem cells (LCSs) in vitro and in vivo. ORP4L was expressed in LSCs but not in normal HSCs and was essential for LSC bioenergetics and survival. [Cell Rep] Full Article | Graphical Abstract CLINICAL RESEARCHInvestigators retrospectively analyzed 2056 patients with multiple myeloma, who underwent autologous-HSC transplantation (auto-HCT) in 2007-2014. They evaluated the 100-day treatment-related mortality and overall survival in two groups; elderly patients who underwent auto-HCT compared with younger patients. [Leukemia] Abstract This single-group, multicenter Phase II study assessed the safety and efficacy of pracinostat combined with azacitidine in patients who were at least 65 years old with newly diagnosed acute myeloid leukemia and who were ineligible for standard induction chemotherapy. [Blood Adv] Abstract | Press Release | Graphical Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSAberrant Wnt Signaling in Multiple Myeloma: Molecular Mechanisms and Targeting Options Functionally, aberrant canonical Wnt signaling plays a dual role in the pathogenesis of multiple myeloma (MM): it mediates proliferation, migration, and drug resistance of MM cells; and MM cells secrete Wnt antagonists that contribute to the development of osteolytic lesions by impairing osteoblast differentiation. [Leukemia] Full Article The authors discuss the biology of the JAK/STAT pathway, with particular focus on STAT5 and its crucial role in the development and progression of hematologic malignancies. Furthermore, they provide a synopsis of potential therapeutic strategies based on STAT5 activity inhibition that may represent an excellent opportunity for drug development in oncohematology. [Oncogene] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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SCIENCE NEWSAutolus Therapeutics plc announced that Professor Persis Amrolia, Consultant in Bone Marrow Transplant at Great Ormond Street Hospital presented updated data from the ongoing Phase I CARPALL trial of AUTO1. [Press release from Autolus Therapeutics plc discussing research presented at the European Hematology Association 1st European CAR T Cell Meeting, Paris] Press Release | |
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INDUSTRY NEWSGamida Cell Ltd. announced an agreement with Editas Medicine, Inc. to evaluate the potential use of Editas Medicine’s CRISPR technology to edit NAM-NK cells, which are natural killer (NK) cells that have been expanded using Gamida Cell’s proprietary nicotinamide-based, or NAM, technology. [Gamida Cell Ltd.] Press Release ADC Therapeutics announced that the first patient has been dosed in a Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-402 plus AstraZeneca’s IMFINZI® in patients with advanced diffuse large B-cell lymphoma, mantle cell lymphoma or follicular lymphoma. [ADC Therapeutics] Press Release Genentech announced that the FDA has accepted the company’s Biologics License Application and granted Priority Review for polatuzumab vedotin in combination with bendamustine plus Rituxan® for the treatment of people with relapsed or refractory diffuse large B-cell lymphoma. [Genentech, Inc.] Press Release CASI Pharmaceuticals, Inc. announced that the NMPA has approved the company’s Clinical Trial Application (CTA) to allow for a confirmatory clinical trial to evaluate the efficacy and safety of ibritumomab tiuxetan injection (ZEVALIN®). [CASI Pharmaceuticals, Inc.] Press Release Poseida Therapeutics Inc. announced that the US Patent and Trademark Office has issued a Notice of Allowance for a patent protecting the method of producing genetically modified T cells with a high percentage of stem cell memory T cells. The company’s lead product candidate, P-BCMA-101, is an autologous CAR-T therapeutic candidate to treat patients with relapsed/refractory multiple myeloma. [Poseida Therapeutics Inc.] Press Release Lilly Completes Acquisition of Loxo Oncology Eli Lilly and Company announced the successful completion of its acquisition of Loxo Oncology, Inc. The acquisition broadens the scope of Lilly’s oncology portfolio into precision medicines through the addition of a pipeline of highly selective potential medicines for patients with genomically defined cancers. [Eli Lilly and Company] Press Release | |
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POLICY NEWSAustralia Dials Back Effort to Control ‘Dual Use’ Research A review of Australian export laws has pushed back against the government’s effort to tighten controls on technologies and research that might have dual military and non-military uses. Australian researchers, who were concerned that sweeping controls would restrict collaborative research, have welcomed the findings. [Nature News] Editorial Trump Science Adviser Calls for More Collaboration Between Industry and Government Kelvin Droegemeier, newly minted science adviser to US President Donald Trump, wants industry to take a larger role in funding research, with the ultimate goal of ushering in a “second golden era” of US science. [Nature News] Editorial
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EVENTSNEW Keystone Symposia: Cancer Stem Cells – Advances in Biology and Clinical Translation Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – RNA Modifications, Hematopoiesis & Cancer (Lund University) Postdoctoral Research Fellow – Development of Lymphoid Cells (Lund University) Chair – Microbiology and Immunology (Indiana University School of Medicine) Postdoctoral Studies – Normal & Malignant Hematopoiesis (Karolinska Institutet) Investigator Positions – Hematologic Malignancies (University of Alabama Birmingham) Postdoctoral Associate – T-ALL Research (University of New Mexico) 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) Assistant Project Scientist – Hematology and Oncology (University of California, Davis) Faculty Positions – Hematology and Oncology (University of California, 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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