Hematopoiesis News Volume 10.43 | Nov 5 2019

TOP STORY

Hematopoietic Stem Cells in Perisinusoidal Niches Are Protected from Aging

By using in vivo long-term label-retention assays investigators demonstrated that aged label-retaining HSCs, which were, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, resided predominantly in perisinusoidal niches. [Nat Cell Biol] Abstract

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In Vivo Generation of Hematopoietic Stem/Progenitor Cells from Bone Marrow-Derived Hemogenic Endothelium

By using experimental embryology and genetic approaches in birds and mice, respectively, researchers documented the discovery of a bone marrow haemogenic endothelium in the late fetus/young adult. These cells were capable of de novo producing a cohort of hematopoietic stem and progenitor cells (HSPCs) in situ that harbored a very specific molecular signature close to that of aortic endothelial cells undergoing endothelial-to-haematopoietic transition or their immediate progenies, i.e., recently emerged HSPCs. [Nat Cell Biol] Abstract | Press Release

SHP2 Inhibition Reduces Leukemogenesis in Models of Combined Genetic and Epigenetic Mutations

Utilizing mouse models of acute myeloid leukemia that recapitulated cardinal features of the human disease and bore a combination of loss-of-function mutations in either Tet2 or Dnmt3a along with expression of Flt3^ITD, scientists showed that inhibition of the protein tyrosine phosphatase SHP2, which is essential for cytokine receptor signaling, by the small molecule allosteric inhibitor SHP099 impaired growth and induced differentiation of leukemic cells without impacting normal hematopoietic cells. [J Clin Invest] Full Article

Lineage Tracing of Acute Myeloid Leukemia Reveals the Impact of Hypomethylating Agents on Chemoresistance Selection

The authors developed an experimental model system using in vitro lineage tracing coupled with exome, transcriptome and in vivo functional readouts to assess the acute myeloid leukemia population dynamics and associated molecular determinants underpinning chemoresistance development. They found that combining standard chemotherapeutic regimens with low doses of DNA methyltransferase inhibitors prevented chemoresistant relapses. [Nat Commun] Full Article

Novel Bicistronic Lentiviral Vectors Correct β-Hexosaminidase Deficiency in Neural and Hematopoietic Stem Cells and Progeny: Implications for In Vivo End Ex Vivo Gene Therapy of GM2 Gangliosidosis

Investigators showed that lentiviral vectors drove the safe and coordinated expression of α- and β-subunits, leading to supranormal levels of β-Hexosaminidase activity with prevalent formation of a functional HexA in SD murine neurons and glia, murine bone marrow-derived hematopoietic stem/progenitor cells, and human SD fibroblasts. [Neurobiol Dis] Abstract

Proteomic Analysis of an Induced Pluripotent Stem Cell Model Reveals Strategies to Treat Juvenile Myelomonocytic Leukemia

Scientists undertook a proteomic assessment of myeloid cells derived from induced pluripotent stem cells obtained from Noonan syndrome patients with PTPN11 mutations, either associated or not associated with increased incidence of juvenile myelomonocytic leukemia. They report that the proteomic perturbations induced by the leukemia-associated PTPN11 mutations were associated with TP53 and NF-ĸb signaling. [J Proteome Res] Abstract

Bmi1 Counteracts Hematopoietic Stem Cell Aging by Repressing Target Genes and Enforcing the Stem Cell Gene Signature

Researchers attempted to ameliorate the age-related decline in HSC function by modulating Bmi1 expression. The forced expression of Bmi1 did not attenuate myeloid-biased differentiation of aged HSCs. However, single cell transplantation assays revealed that the sustained expression of Bmi1 augmented the multi-lineage repopulating capacity of aged HSCs. [Biochem Biophys Res Commun] Abstract | Graphical Abstract

CLINICAL RESEARCH

Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced Intensity Allogeneic Hematopoietic Cell Transplantation

Scientists retrospectively reviewed 1583 consecutive patients receiving reduced intensity conditioning hematopoietic stem cell transplantation at the Dana-Farber Cancer Institute between 2007-2017 and ascertained 26 cases of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). The median day of VOD/SOS onset was 26 days and the cumulative incidence at day 50 was 1.6%. [Biol Blood Marrow Transplant] Abstract

Hematopoietic Stem Cell Transplantation without the Use of Blood Components by the Patients Choice- Experience of Two Brazilian Centers

Scientists developed 21 transplants without transfusion support in 19 patients admitted to two Brazilian transplant centers. The patients were subjected to stem cell mobilization and different conditioning regimens. No mortality related to the procedure was found among the transplant recipients. [Biol Blood Marrow Transplant] Abstract

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Clonal Hematopoiesis in Human Aging and Disease

The process of mutation and clonal selection is likely to be universal across all organs and tissues. Understanding the causes and consequences of clonal hematopoiesis may provide a framework to understand this process, and aging, more broadly. [Science] Abstract

CD19 Chimeric Antigen Receptor-T Cells in B-Cell Leukemia and Lymphoma: Current Status and Perspectives

Anti-CD19 chimeric antigen receptor-T cells has proved to be highly effective in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia and specific histologic subtypes of B-cell non-Hodgkin lymphomas. The authors summarize the current available research evidence in this field, with a special focus on the different challenges faced by treating physicians, and also provide future perspectives. [Leukemia] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.

MD Anderson and Takeda Announce Collaboration to Accelerate the Development of Clinical-Stage, Off-the-Shelf CAR NK-Cell Therapy Platform

The University of Texas MD Anderson Cancer Center and Takeda Pharmaceutical Company Limited announced an exclusive license agreement and research agreement to develop cord blood-derived chimeric antigen receptor-directed natural killer-cell therapies, ‘armored’ with IL-15, for the treatment of B-cell malignancies and other cancers. [The University of Texas MD Anderson Cancer Center] Press Release

Allogene Therapeutics and Notch Therapeutics Announce Collaboration to Research and Develop Induced Pluripotent Stem Cell (iPSC)-Derived Allogeneic Therapies for Hematologic Cancer Indications

Allogene Therapeutics, Inc. and Notch Therapeutics Inc. announced an exclusive worldwide collaboration and license agreement to research and develop iPSC AlloCAR™ therapy products for initial application in non-Hodgkin lymphoma, leukemia and multiple myeloma. [Allogene Therapeutics, Inc.] Press Release

NexImmune Receives IND Clearance for Phase I/II Trial in Acute Myeloid Leukemia / Myelodysplastic Syndrome

NexImmune received Investigational New Drug (IND) clearance for the company’s first cellular therapy product. NEXI-001 is being developed for the treatment of acute myeloid leukemia or myelodysplastic syndrome patients with relapsed disease after an allogeneic hematopoietic cellular transplant. [NexImmune] Press Release

First Patient Dosed with Off-the-Shelf UCARTCS1 Product Candidate for Relapsed/Refractory Multiple Myeloma

Cellectis announced the company has dosed the first patient in its UCARTCS1 clinical trial, MELANI-01, the first allogeneic off-the-shelf CAR-T product candidate the FDA has cleared to enter into clinical development for relapsed/refractory multiple myeloma. [Cellectis] Press Release

Autolus Therapeutics Receives FDA Orphan Drug Designation for AUTO1 for Treatment of Acute Lymphoblastic Leukemia

Autolus Therapeutics plc announced that the FDA has granted AUTO1 orphan drug designation for treatment of acute lymphoblastic leukemia (ALL) patients. [Autolus Therapeutics plc] Press Release

Trainees Often Ghostwrite PIs’ Peer Reviews: Survey

Many graduate students and postdocs write or help compose peer reviews their advisors are invited to provide, according to a survey of nearly 500 early-career researchers published on October 31^st in eLife. And often they do so without disclosing that fact to the journal – a practice that the survey authors consider to be ghostwriting. [The Scientist] Editorial

Trump Nominates MD Anderson’s Stephen Hahn to Lead FDA

President Trump announced his intent to nominate Dr. Stephen Hahn to lead the FDA. Dr Stephen Hahn is the chief medical executive at MD Anderson Cancer Center in Houston. While he is an accomplished physician and researcher, he has never worked in government, leaving his potential FDA agenda a mystery. [STAT News] Editorial

NEW Hematopoiesis
April 3-7, 2020
Big Sky, Montana, United States

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NEW Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.)

NEW Senior Scientist – Leukemia Stem Cells (MD Anderson Cancer Center)

Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine)

Associate/Professor – Hematology & Oncology (UC Davis School of Medicine)

PhD Project – Physical Biology of Blood Stem Cells (University of York)

Postdoctoral Fellowship (Versiti Blood Research Institute)

Faculty Positions – Gene Editing (Indiana University School of Medicine)

Postdoctoral Fellowship – Hematopoietic Cell Transplantation (University of Maryland)

Postdoctoral Scholar – Hematopoietic Cells (Penn State University)

Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer)

Postdoctoral Positions – Stem Cell Biology, Cancer Biology, and Epigenetics (Baylor College of Medicine)

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