Hematopoiesis News Volume 9.46 | Nov 20 2018

TOP STORY

VCAM-1⁺ Macrophages Guide the Homing of HSPCs to a Vascular Niche

Using advanced live imaging and a cell-labelling system, scientists performed high-resolution analyses of the hematopoietic stem and progenitor cell (HSPC) homing in caudal hematopoietic tissue of zebrafish, and revealed the role of the vascular architecture in the regulation of HSPC retention. [Nature] Abstract

(Ranked by impact factor of the journal)

In Vivo Hematopoietic Stem Cell Gene Therapy Ameliorates Murine Thalassemia Intermedia

HDAd5/35⁺⁺ vectors for in vivo gene therapy of thalassemia had a unique capsid that targeted primitive hematopoietic stem/progenitor cells through human CD46, a relatively safe SB100X transposase-based integration machinery, a micro-LCR driven gamma-globin gene and, a MGMT(P140K) system that allowed for increasing the therapeutic effect by short-term treatment with low-dose O6BG/BCNU. [J Clin Invest] Abstract

In Vitro Conversion of Adult Murine Endothelial Cells to Hematopoietic Stem Cells

Researchers described a stepwise approach that converts adult murine endothelial cells (ECs) to HSCs, termed ‘reprogrammed ECs into hematopoietic stem and progenitor cells’ (rEC-HSPCs). They also described functional in vitro and in vivo assays that can be used to demonstrate that rEC-HSPCs are competent for clonal engraftment and possess multi-lineage reconstitution potential, including antigen-dependent adaptive immune function. [Nat Protoc] Abstract

Attenuation of PKCδ Enhances Metabolic Activity and Promotes Expansion of Blood Progenitors

Scientists report that protein kinase C delta (PKCδ) is a critical regulator of adult hematopoietic stem and progenitor cell (HSPC) number and function that couples the proliferative and metabolic activities of HSPCs. PKCδ‐deficient mice showed a pronounced increase in HSPC numbers, increased competence in reconstituting lethally irradiated recipients, enhanced long‐term competitive advantage in serial transplantation studies, and an augmented HSPC recovery during stress. [EMBO J] Full Article | Graphical Abstract

Constitutive Activation of the Canonical NF-κB Pathway Leads to Bone Marrow Failure and Induction of Erythroid Signature in Hematopoietic Stem Cells

Investigators demonstrated that deregulated canonical NF-κB signals in HSCs caused a complete depletion of HSC pool, pancytopenia, bone marrow failure, and premature death. [Cell Rep] Full Article | Graphical Abstract

In Vitro and In Vivo Evaluation of Possible Pro-Survival Activities of PGE2, EGF, TPO and FLT3L on Human Hematopoiesis

EGF was neither able to protect human stem and progenitor cells in vitro nor to promote hematopoietic regeneration following sublethal irradiation in vivo. PGE2 significantly reduced in vitro apoptotic susceptibility of human CD34⁺ cells to taxol and etoposide. [Haematologica] Abstract | Full Article

Zebrafish miR-462-731 Regulates Hematopoietic Specification and pu.1-Dependent Primitive Myelopoiesis

Scientists unveiled a previously unrecognized role of miR-462-731 in BMP/Smad signaling mediated hematopoietic specification of mesodermal progenitors and demonstrated a miR-462-731 mediated regulatory mechanism driving primitive myelopoiesis in the ALPM. They showed a requirement for miR-462-731 in regulating arterial-venous specification and definitive HSC production. [Cell Death Differ] Abstract

VE-Cadherin and ACE Co-Expression Marks Highly Proliferative Hematopoietic Stem Cells in Human Embryonic Liver

By using a combination of four endothelial and hematopoietic surface markers i.e. the endothelial-specific marker VE-cadherin, the pan-leukocyte antigen CD45, the hemato-endothelial marker CD34 and the Angiotensin-Converting Enzyme, investigators identified distinct HSCP subsets, among them, a population co-expressing the four markers that uniquely harbored an outstanding proliferation potential both ex vivo and in vivo. [Stem Cells Dev] Abstract

CLINICAL RESEARCH

Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Non-Randomized, Open-Label, Phase II Study

Azacitidine-nivolumab therapy produced an encouraging response rate and overall survival in patients with relapsed/refractory-AML, particularly in HMA-naive and Salvage-1 patients. Pretherapy bone marrow aspirate and peripheral blood CD3 percentage may be biomarkers for patient selection. [Cancer Discov] Abstract | Press Release | Full Article

Cytarabine + G-CSF Is More Effective Than Cyclophosphamide + G-CSF as a Stem Cell Mobilization Regimen in Multiple Myeloma

Researchers concluded that mobilization with cytarabine plus granulocyte-colony stimulating factor (G-CSF) is very effective with acceptable toxicity and could be considered in multiple myeloma patients with planned or expected higher numbers of transplantations. [Bone Marrow Transplant] Abstract

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Advances in the Treatment of Sickle Cell Disease

Currently, red blood cell transfusion and hydroxyurea are the major disease-modifying therapies available for sickle cell disease. Hematopoetic stem cell transplant is curative, but barriers to treatment are substantial and include a lack of suitable donors, immunologic transplant rejection, long-term adverse effects, prognostic uncertainty, and poor end-organ function, which is especially problematic for older patients. [Mayo Clin Proc] Full Article

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

Immunotherapy Combination and Chemotherapy Show Encouraging Results in Phase II Acute Myeloid Leukemia Study

A triple therapy combining two immune checkpoint inhibitors with the standard-of-care chemotherapy, a hypomethylating agent called azacitidine, has shown promising results for treatment of relapsed or refractory acute myeloid leukemia. [Press release from The University of Texas MD Anderson Cancer Center discussing research to be presented at the 60^th American Society of Hematology Annual Meeting & Exposition, San Diego] Press Release

City of Hope Doctors Present New Research on CAR T Cell Therapy, Bone Marrow Transplants and Other Treatments for Blood Cancers

City of Hope announced that it will present data on new findings on immunotherapies, including CAR T cell therapy, bone marrow transplants and other treatments for blood cancers. [Press release from City of Hope (Business Wire, Inc.) discussing research to be presented at the 60^th American Society of Hematology Annual Meeting & Exposition, San Diego] Press Release

ERYTECH Partners with New York Blood Center for Red Blood Cell Supply and Research

ERYTECH Pharma announced a strategic partnership with New York Blood Center (NYBC) for red blood cell supply and research. The partnership encompasses NYBC becoming a long-term supplier of donor red blood cells (RBCs) to ERYTECH, enabling ERYTECH to diversify and broaden its supply of RBC source materials for the production of eryaspase and future product candidates derived from its proprietary ERYCAPS^® platform as the company ramps up clinical development. [ERYTECH Pharma (GlobeNewswire, Inc.)] Press Release

The Leukemia & Lymphoma Society (LLS) Fuels the Next Generation of Cancer Research Committing More Than $188 Million in Funding

Driving the dizzying pace of breakthroughs in blood cancer treatments, The Leukemia & Lymphoma Society (LLS) announced $42 million for 80 blood cancer research teams around the world. This latest infusion of funding by LLS, the world’s largest nonprofit devoted to curing blood cancers, brings the organization’s current commitment to more than $188 million in multi-year grants, supporting more than 240 top scientific investigators at the world’s most prestigious cancer institutions. [The Leukemia & Lymphoma Society] Press Release

FDA Approves Novartis Drug Promacta^® for First-Line SAA and Grants Breakthrough Therapy Designation for Additional New Indication

Novartis announced that the FDA has expanded the label for Promacta^® to include first-line treatment for adults and pediatric patients two years and older with severe aplastic anemia (SAA) in combination with standard immunosuppressive therapy. [Novartis] Press Release

National Institute for Health and Care Excellence (NICE) Recommends Jazz Pharmaceuticals’ Vyxeos^® (Daunorubicin and Cytarabine) for Adults with Specific Types of Secondary Acute Myeloid Leukemia (AML)

Jazz Pharmaceuticals plc announced that NICE has published a Final Appraisal Determination recommending Vyxeos^® 44 mg/100 mg powder for concentrate for solution for infusion for routine use on the National Health Service in England and Wales for the treatment of adults with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes. [Jazz Pharmaceuticals plc] Press Release

FDA Approves Gamifant^® (Emapalumab-lzsg), the First and Only Treatment Indicated for Primary Hemophagocytic Lymphohistiocytosis (HLH)

Sobi and Novimmune SA announced that the FDA has approved Gamifant^®, an interferon gamma blocking antibody for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. [Sobi] Press Release

uniQure Announces Initial Topline Data from Dose-Confirmation Study of AMT-061 in Patients with Hemophilia B

uniQure N.V. announced initial clinical data in patients treated in the company’s Phase IIb dose-confirmation study of AMT-061, an investigational AAV5-based gene therapy containing a patent-protected FIX-Padua variant, for the treatment of patients with severe and moderately severe hemophilia B. [uniQure N.V.] Press Release

Amgen Receives CHMP Positive Opinion to Expand Use of BLINCYTO^® (Blinatumomab) in Patients with Minimal Residual Disease-Positive B-Cell Precursor Acute Lymphoblastic Leukemia

Amgen announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion to expand the current indication for BLINCYTO^® monotherapy to include adult patients with Philadelphia chromosome negative CD19 positive B-cell precursor acute lymphoblastic leukemia in first or second complete remission with minimal residual disease greater than or equal to 0.1 percent. [Amgen] Press Release

FDA Clears Way for Trials of FOR46 in Late-Stage Multiple Myeloma, Prostate Cancer

The FDA has allowed Fortis Therapeutics’ antibody-drug conjugate FOR46 to begin testing in a Phase I clinical trial as a therapy for late-stage multiple myeloma. [Myeloma Research News] Press Release

St. Jude Announces Extensive Resource to Advance Leukemia Research

St. Jude Children’s Research Hospital announced the availability of one of the world’s largest collections of leukemia samples from children and adults. The effort, called PROPEL (Public Resource of Patient-Derived and Expanded Leukemias), aims to advance fundamental research on the biology of leukemia and to help develop cures by sharing unique patient-derived xenograft samples with researchers around the world. [St. Jude Children’s Research Hospital] Press Release

Sernova Highlights Achievements from the HemAcure Consortium in Developing a Novel Cell-Based Therapy for Hemophilia A

Sernova Corp. highlights the achievements in developing a novel cell-based therapy in combination with Sernova’s Cell Pouch^™ for treatment of Hemophilia A. [Sernova Corp. (TheNewswire)] Press Release

Duke University to Settle Case Alleging Researchers Used Fraudulent Data to Win Millions in Grants

Duke University in Durham, North Carolina, is on the verge of settling a case brought by a former employee who claims the university included faked data in applications and reports for federal grants worth nearly $200 million. [ScienceInsider] Editorial

French Science Behemoth Launches Research-Integrity Office

France’s national research center, the CNRS, has announced plans to create its first office of research integrity to investigate scientific misconduct and promote good research practice. [Nature News] Editorial

In Reversal, NSF Lifts Proposal Limits on Biologists

In a reversal, the National Science Foundation (NSF) will no longer restrict researchers to only one proposal submission per year to the biology directorate’s three core tracks in which they are listed as a principal investigator (PI) or co-PI. [ScienceInsider] Editorial

NEW Lorne Cancer Conference 2019
February 14-16, 2019
Lorne, Australia

Visit our events page to see a complete list of events in the community.

NEW Research Technologist – Hematopoietic (STEMCELL Technologies Inc.)

Staff Scientist – Hematology (St. Jude Children’s Research Hospital)

Assistant Project Scientist – Hematology and Oncology (University of California, Davis)

Postdoctoral Scientist – Hematology (University Medical Center Freiburg)

Research Scientist – Hematological Malignancies (MD Anderson Cancer Center)

Postdoctoral Position – Gene Modification in HSCs (University of Wisconsin-Madison)

Faculty Positions – Hematology and Oncology (UC Davis)

Postdoctoral Position or PhD Student – Bioinformatics in Leukemia (RWTH Aachen Medical School)

Assistant, Associate or Full Professors – Malignant Hematopoiesis (Cincinnati Children’s Research Medical Center)

Postdoctoral Fellows – Hematopoiesis and Blood Disorders (Cleveland Clinic Lerner Research Institute)

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