Hematopoiesis News Volume 11.17 | May 5 2020

TOP STORY

Differentiation of Transplanted Hematopoietic Stem Cells Tracked by Single-Cell Transcriptomic Analysis

Using single-cell RNA sequencing, the authors first obtained the transcriptome-based classifications of 28 hematopoietic cell types. They then applied them in conjunction with functional assays to track the dynamic changes of immunophenotypically purified HSCs in irradiated recipients within the first week after transplantation. [Nat Cell Biol] Abstract

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The Transcription Factor ETS1 Is an Important Regulator of Human NK Cell Development and Terminal Differentiation

By generating ETS1-deficient human embryonic stem cells and by expressing the dominant-negative ETS1 p27 isoform in cord blood hematopoietic progenitor cells, investigators showed that the transcription factor ETS1 was critically required for human natural killer (NK) cell differentiation. [Blood] Abstract

Hematopoietic Stem Cell Function in β-Thalassemia Is Impaired and Is Rescued by Targeting the Bone Marrow Niche

Researchers report that HSCs in thalassemic mice had an impaired function, caused by the interaction with an altered bone marrow niche. [Blood] Abstract

Mesenchymal Niche Remodeling Impairs Hematopoiesis via Stanniocalcin 1 in Acute Myeloid Leukemia

To mimic acute myeloid leukemia (AML) infiltration and dissect the cellular crosstalk in human bone marrow, scientists established humanized ex vivo and in vivo niche models comprising AML cells, normal hematopoietic stem and progenitor cells (HSPCs), and mesenchymal stromal cells. Both models replicated the suppression of phenotypically defined HSPC differentiation without affecting their viability. [J Clin Invest] Full Article | Graphical Abstract

Mesenchymal PGD₂ Activates an ILC2-Treg Axis to Promote Proliferation of Normal and Malignant HSPCs

Scientists showed that mesenchymal stromal cells (MSCs) from patients with acute myeloid leukemia or normal MSCs overexpressing cyclooxygenase 2 (COX2) promoted proliferation of co-cultured hematopoietic stem and progenitor cells (HSPCs), which could be prevented by treatment with COX2 knockdown or TM30089, a specific antagonist of the PGD₂ receptor CRTH2. [Leukemia] Abstract

Anti-Human CD117 CAR T-Cells Efficiently Eliminate Healthy and Malignant CD117-Expressing Hematopoietic Cells

Researchers successfully generated anti-CD117 CAR T-cells from healthy donors and acute myeloid leukemia patients. Anti-CD117 CAR T-cells efficiently targeted healthy and leukemic CD117-positive cells in vitro. In mice xenografted with healthy human hematopoiesis, they eliminated CD117-expressing, but not CD117-negative human cells. [Leukemia] Abstract

Natural Estrogens Enhance the Engraftment of Human Hematopoietic Stem and Progenitor Cells in Immunodeficient Mice

Investigators showed that human hematopoietic stem and progenitor cell subsets expressed estrogen receptors, and whose signaling was activated by E2 and E4 on these cells. Additionally, these natural estrogens caused different effects on human progenitors in vitro. [Haematologica] Abstract

Increasing CRISPR Efficiency and Measuring Its Specificity in Hematopoietic Stem and Progenitor Cells Using a Clinically Relevant System

The authors aimed to optimize on-target ex vivo genome editing using the CRISPR-Cas9 system in CD34⁺ hematopoietic stem and progenitor cells and to create a clear workflow for precise identification of off-target effects. [Mol Ther Methods Clin Dev] Abstract | Graphical Abstract | Full Article

EDAG Mediates Hsp70 Nuclear Localization in Erythroblasts and Rescues Dyserythropoiesis in Myelodysplastic Syndrome

Researchers found the hematopoietic transcriptional regulator, erythroid differentiation‐associated gene (EDAG), to be a novel binding partner of Hsp70 that formed a protein complex with Hsp70 and GATA‐1 during human normal erythroid differentiation. [FASEB J] Abstract

CLINICAL RESEARCH

Comparison of Reduced-Intensity Conditioning Regimens in Patients with Acute Lymphoblastic Leukemia > 45 Years Undergoing Allogeneic Stem cell Transplantation—A Retrospective Study by the Acute Leukemia Working Party of EBMT

Scientists retrospectively analyzed 417 patients > 45 years with acute lymphoblastic leukemia (ALL) in first complete remission who underwent a matched sibling or unrelated allogeneic hematopoietic stem cell transplantation and compared outcomes between fludarabine/busulfan, fludarabine/melphalan, and fludarabine-TBI conditioning. [Bone Marrow Transplant] Abstract

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The Role of Deubiquitinating Enzymes in Hematopoiesis and Hematological Malignancies

The authors focus on recent discoveries about the physiological roles of deubiquitinating enzymes (DUBs) in hematopoiesis, erythropoiesis, and angiogenesis and discuss the DUBs associated with common hematological disorders and malignancies, which are potential therapeutic drug targets. [Cancers] Abstract | Download Full Article

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TG Therapeutics Announces Positive Topline Results from the UNITY-CLL Phase III Study Evaluating the Combination of Umbralisib and Ublituximab (U2) for the Treatment of Patients with Chronic Lymphocytic Leukemia

TG Therapeutics, Inc. announced positive topline results from the global UNITY-CLL Phase III trial evaluating the combination of umbralisib plus ublituximab compared to obinutuzumab plus chlorambucil in patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia (CLL). [TG Therapeutics, Inc.] Press Release

Genmab Announces US FDA Approval of Subcutaneous Formulation of Daratumumab, DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj), for the Treatment of Patients with Multiple Myeloma

Genmab A/S announced that the FDA has approved the use of the subcutaneous formulation of daratumumab, DARZALEX FASPRO™. DARZALEX FASPRO is approved for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant. [Genmab A/S] Press Release

The Pandemic’s Effects on Recruiting International STEM Trainees

Pandemic-related concerns that have arisen for science trainees—shuttered labs, research and education delays, anxiety—are applicable across the board. But international graduate students and postdocs face a suite of unique challenges that raise uncertainty about recruiting and supporting this critical group of researchers in the future. [The Scientist] Editorial

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NEW Postdoctoral Position – Tumor Immunology (University of Maryland)

Postdoctoral Position – Leukemia (Josep Carreras Leukaemia Research Institute)

Postdoctoral Position – Immunology/Molecular Biology (NIH National Heart, Lung, and Blood Institute)

Postdoctoral Associate – Hematopoiesis (The Jackson Laboratory)

PhD Position – Leukemic Stem Cells and Metabolism (University of Bern)

Research Fellow – Cancer Biology (Dana Farber Cancer Institute)

Scientist – Cancer Immunotherapy (Asgard Therapeutics and Lund University)

Postdoctoral Fellow – Hematopoiesis Research (Harvard Medical School)

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

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

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