Hematopoiesis News 10.28 July 23, 2019 | |
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TOP STORYLeukemia stem cells protect themselves against the immune defense by suppressing a target molecule for killer cells. This protective mechanism can be tricked with drugs. Scientists from Basel, Tübingen and Heidelberg describe the new therapeutic approaches that can possibly be derived from these results. [Press release from German Cancer Consortium discussing online prepublication in Nature] Press Release | Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Targeting Cell Membrane HDM2: A Novel Therapeutic Approach for Acute Myeloid Leukemia The authors showed that membrane human double minute 2 (mHDM2) was exclusively expressed on human and mouse AML blasts, including leukemia stem cell-enriched subpopulations, but not on normal HSCs. Higher mHDM2 levels in AML blasts were associated with leukemia-initiating capacity, quiescence, and chemoresistance. [Leukemia] Abstract Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation GMB-475 reduced viability and increased apoptosis in primary chronic myeloid leukemia (CML) CD34+ cells, with no effect on healthy CD34+ cells at identical concentrations. GMB-475 degraded BCR-ABL1 and reduced cell viability in primary CML stem cells. [Cancer Res] Abstract Integrin-α3 Is a Functional Marker of Ex Vivo Expanded Human Long-Term Hematopoietic Stem Cells Researchers identified integrin-α3 (ITGA3) as a marker of cultured human HSCs. They showed that ITGA3 expression was sufficient to separate the primitive EPCR+CD90+CD133+CD34+CD45RA− HSC population into two functionally distinct fractions presenting mostly short-term and both short-term and long-term repopulating potential. [Cell Rep] Full Article | Graphical Abstract Investigators demonstrated that alterations in B cell receptor (BCR) signaling dynamics underlie the progression of B cells toward malignancy. They revealed emergent dynamic features—bimodality, hypersensitivity, and hysteresis—in the BCR signaling pathway of primary chronic lymphocytic leukemia B cells. [Cell Rep] Full Article | Graphical Abstract The capsid-associated tegument protein pp150 was released from maturing endosomes and migrated to the nucleus, whereas other tegument proteins, including pp71, remained endosome associated in the cytoplasm. The inhibition of macropinocytosis impaired entry, thereby diminishing latency-associated transcription and reducing viral reactivation. [J Virol] Abstract The authors confirmed that MN1 overexpression in the hematopoietic lineage was sufficient to drive myeloid leukemia. In addition, they showed that T-cell specific activation of MN1 in combination with loss of Pten increased tumor penetrance and stimulated the formation of Lyl1+ murine T-cell lymphoblastic leukemias or lymphomas. [Sci Rep] Full Article LW-213 treatment degraded the downstream proteins of BCR-ABL1, such as oncoproteins AKT, STAT3/5 in chronic myeloid leukemia (CML) cells, which was blocked by NH4Cl. In primary CML cells and CD34+ stem cells, LW-213 maintained its pro-apoptotic activity. [Acta Pharmacol Sin] Abstract CLINICAL RESEARCHResearchers applied single molecule-sensitive direct stochastic optical reconstruction microscopy, and demonstrated CD19 expression on a fraction of myeloma cells in 10 out of 14 patients. In contrast, flow cytometry detected CD19 in only two of these ten patients, on a smaller fraction of cells. Treatment with CD19 CAR-T in vitro resulted in elimination of CD19-positive myeloma cells, including those with <100 CD19 molecules per cell. [Nat Commun] Full Article Scientists investigated whether the addition of sorafenib to intensive induction chemotherapy improved outcomes in patients with FLT3-internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML). In total, 183 patients who were newly diagnosed with FLT3-ITD-mutated AML between February 2001 and December 2017 were identified. [Cancer] Abstract Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News. | |
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REVIEWSThe Genetics of Human Hematopoiesis and Its Disruption in Disease The authors discuss advances in functionally characterizing common variants associated with blood cell traits and discuss therapeutic insights, such as the discovery of BCL11A as a modulator of fetal hemoglobin expression. Finally, as genetic techniques continue to evolve, they discuss the prospects, challenges, and unanswered questions that lie ahead in this burgeoning field. [EMBO Mol Med] Full Article Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSThe Humanigen license covers various patent applications filed by University of Zurich which complement and broaden Humanigen’s leadership position in the application of granulocyte macrophage-colony stimulating factor (GM-CSF) and expand Humanigen’s development platform to include improving allogeneic hematopoietic stem cell therapy. [Humanigen, Inc.] Press Release Actinium Achieves Fifty Percent Enrollment in the Pivotal Phase III SIERRA Trial for Iomab-B Actinium Pharmaceuticals, Inc. announced that the 75th patient has been treated in the pivotal Phase III SIERRA trial of Iomab-B, thus achieving 50 percent patient enrollment for the trial. [Actinium Pharmaceuticals, Inc.] Press Release CTI BioPharma Corp. announced the outcome of a Type B, End-of-Phase-IIa meeting with the FDA for the continued development of its investigational myelofibrosis treatment candidate, pacritinib. Following this meeting, CTI plans to evaluate 200 mg of pacritinib administered twice daily in 180 patients with myelofibrosis and severe thrombocytopenia. [CTI BioPharma Corp.] Press Release MacroGenics Provides Update on Flotetuzumab Program in Acute Myeloid Leukemia MacroGenics, Inc. announced that it plans to advance the development of flotetuzumab, its investigational bispecific CD123 x CD3 DART® molecule, in patients with primary refractory acute myeloid leukemia, a difficult-to-treat patient population. [MacroGenics, Inc.] Press Release Moleculin Announces Annamycin in Acute Myeloid Leukemia in Poland Advances to 3rd Cohort Moleculin Biotech, Inc. announced additional positive interim safety and efficacy data from its ongoing open label, single arm Phase I/II study of annamycin in Poland. Three patients were treated at dose level of 150 mg/m2 with no drug-related adverse events, including no signs of cardiotoxicity. [Moleculin Biotech, Inc.] Press Release Ascentage Pharma announced that the company was notified by the FDA on the clearance of the Investigational New Drug application which allows the company to initiate its Phase Ib clinical trial of HQP1351, a novel drug candidate developed by Ascentage Pharma, for the treatment of patients with tyrosine kinase inhibitor-resistant chronic myeloid leukemia in the United States. [Ascentage Pharma (PR Newswire Association LLC.)] Press Release CStone Pharmaceuticals announced that it has received approval from the China National Medical Products Administration to initiate a Phase I bridging registrational study of ivosidenib for the treatment of relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation. [CStone Pharmaceuticals] Press Release Akebia Therapeutics, Inc. announced that Mitsubishi Tanabe Pharma Corporation (MTPC), its development and commercialization collaboration partner in Japan for vadadustat, Akebia’s investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor, has submitted a Japanese New Drug Application to the Ministry of Health, Labor and Welfare in Japan for manufacturing and marketing approval of vadadustat as a treatment for anemia due to chronic kidney disease. [Akebia Therapeutics, Inc.] Press Release | |
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POLICY NEWSBudget Deal Raises Hopes for US Research Agencies A new budget deal between the White House and congressional leaders means US research agencies could receive increases on the order of the 4% to 5% that Democrats have already proposed for next year. [ScienceInsider] Editorial What Boris Johnson’s Leadership Could Mean for Science Boris Johnson has been selected as the United Kingdom’s new prime minister — and is poised to lead the country out of the European Union (EU). At the forefront of many scientists’ minds are questions about how Johnson’s leadership, including his support for a ‘no deal’ Brexit, will affect research. They fear that British science has much to lose from a messy departure from the EU. [Nature News] Editorial
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EVENTSNEW XVIII International Workshop on CLL (iwCLL) Meeting Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – Genome Editing of Hematopoietic Stem Cells (Bar-Ilan University) Postdoctoral Position – Advanced Proteomics & Erythropoiesis (Lund University) Postdoctoral Fellow – Acute Myeloid Leukemia Research (University of Gothenburg) Postdoctoral Position – Hematopoietic Stem Cell Biology (Columbia University Irving Medical Center) Postdoctoral Position – Leukemia Research (University of California, San Francisco) Postdoctoral Fellow – Hematopoietic Stem Cell Niche in Leukemia (Erasmus Medical Center) Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California) Senior Lecturer Positions – Clinical Oncology or Hematology (Karolinska Institutet) Research Fellow – Hematology, Blood-Disorders & Stem Cell Biology (New York Blood Center) 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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