Hematopoiesis News Volume 10.10 | Mar 19 2019

TOP STORY

Ptpn21 Controls Hematopoietic Stem Cell Homeostasis and Biomechanics

Researchers showed that deletion of Ptpn21, a protein tyrosine phosphatase highly expressed in HSCs, induced stem cell egress from the niche due to impaired retention within the bone marrow. Ptpn21^−/− HSCs exhibited enhanced mobility, decreased quiescence, increased apoptosis, and defective reconstitution capacity. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

CD8⁺ T Cells Expand Stem and Progenitor Cells in Favorable but Not Adverse Risk Acute Myeloid Leukemia

Functionally, CD8⁺ T cells in favorable acute myeloid leukemia (AML) induced the expansion of leukemia stem/progenitor cells (LSPCs) by stimulating the autocrine production of important hematopoietic cytokines such as interleukin-3. In contrast, LSPCs in aggressive AML were characterized by a higher activation of stemness/proliferation-related pathways and develop independent of BM CD8⁺ T cells. [Leukemia] Full Article

Deubiquitylase USP7 Regulates Human Terminal Erythroid Differentiation by Stabilizing GATA1

Mechanistically, USP7 deficiency led to decreased GATA1 protein level that could be reversed by proteasome inhibitors. Furthermore, USP7 interacted directly with GATA1 and catalyzed the removal of K48-linked polyubiquitylation chains conjugated onto GATA1, thereby stabilizing GATA1 protein. [Haematologica] Abstract

Genetic Disarray Follows Mutant KLF1-E325K Expression in a Congenital Dyserythropoietic Anemia Patient

Researchers expanded erythroid cells from a patient’s peripheral blood and analyzed its global expression pattern. They found that a large number of erythroid pathways were disrupted, particularly those related to membrane transport, globin regulation, and iron utilization. The altered genetics lead to significant deficits in differentiation. [Haematologica] Abstract

miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma

Scientists explored the effects of miR-125b and its chemically modified analogues in modulating cell viability and cancer-associated molecular pathways, also focusing on the functional aspects of stress adaptation (autophagy and senescence), as well as programmed cell death (apoptosis). [Mol Ther Nucleic Acids] Abstract | Full Article

Targeting the Thioredoxin System as a Novel Strategy against B Cell Acute Lymphoblastic Leukemia

The authors found that auranofin and adenanthin, inhibitors of the thioredoxin system antioxidant enzymes, effectively killed B cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines and pediatric and adult BCP-ALL primary cells, including primary cells co-cultured with bone marrow-derived stem cells. [Mol Oncol] Abstract | Full Article

miR-125a Enhances Self-Renewal, Lifespan, and Migration of Murine Hematopoietic Stem and Progenitor Cell Clones

Investigators showed that miR-125a, at the single cell level, could expand murine long-term repopulating HSCs. In addition, miR-125a increased clone longevity, clone size and clonal contribution to hematopoiesis. [Sci Rep] Full Article

A Cetuximab-Mediated Suicide System in CAR-Modified Hematopoietic Stem Cells for Cancer Therapy

In vitro, gene-modified HSCs were differentiated into myeloid cells to allow transgene expression. Antibody-dependent cell-mediated cytotoxicity assay was used incubating target cells with leukocytes and monoclonal antibody cetuximab to determine percentage of surviving cells. [Hum Gene Ther] Abstract

Augmentation of iNOS Expression in Myeloid Progenitor Cells Expedites Neutrophil Differentiation

The authors observed that iNOS overexpression led to increased neutrophilic differentiation in K562 cells; more specifically an early and accelerated neutrophilic differentiation was spotted in iNOS-overexpressing K562 cells. [J Leukoc Biol] Abstract

KLF1 Mutation E325K Induces Cell-Cycle Arrest in Erythroid Cells Differentiated from Congenital Dyserythropoietic Anemia (CDA) Patient-Specific Induced Pluripotent Stem Cells

The authors recently diagnosed a female patient with type IV CDA with the identical missense mutation. To understand the mechanism underlying the dyserythropoiesis caused by the mutation, they generated induced pluripotent stem cells from the CDA patient (CDA-iPSCs). The erythroid cells differentiated from CDA-iPSCs displayed multinucleated morphology, absence of CD44, and dysregulation of KLF1 target gene expression. [Exp Hematol] Full Article

CLINICAL RESEARCH

Increased Methylation Upstream of the MEG3 Promotor Is Observed in Acute Myeloid Leukemia Patients with Better Overall Survival

Methylation results were compared with patient response to first-round induction therapy and overall survival. Multivariable analysis was employed to identify independent prognostic factors for patient overall survival in acute myeloid leukemia. [Clin Epigenetics] Full Article

Comparison between Upfront Transplantation and Different Pre-Transplant Cytoreductive Treatment Approaches in Patients with High-Risk MDS and Secondary AML

Investigators retrospectively analyzed the outcome of 165 patients with MDS and excess blasts and secondary AML according to pre-transplant strategy. Sixty-seven patients were directly transplanted, while 98 patients had received pre-transplant cytoreductive treatment resulting in a significantly higher CR rate in the CTX group. [Biol Blood Marrow Transplant] Abstract

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Connections between Clonal Hematopoiesis, Cardiovascular Disease, and Cancer

Current literature suggests that patients with clonal hematopoiesis (CH) have a higher risk of subsequent hematological malignant conditions and mortality attributable to excess cardiovascular disease (CVD). The authors discuss the association of cancer with CVD with CH as a potential unifying factor. [JAMA Cardiology] Abstract

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

Stemline Therapeutics to Participate in Panel on Myeloid Tumors

Stemline Therapeutics, Inc. announced that Ivan Bergstein, M.D., Stemline’s CEO, was selected to participate as a panelist on “The Brave New World of Myeloid Tumors.” [Press release from Stemline Therapeutics, Inc. discussing research presented at the 31^st Annual ROTH Conference, Laguna Niguel] Press Release

AbbVie Provides Update on VENCLEXTA^®/VENCLYXTO^® (Venetoclax) Multiple Myeloma Program

AbbVie announced the FDA has placed a partial clinical hold on all clinical trials evaluating venetoclax for the investigational treatment of multiple myeloma. The partial clinical hold follows a review of data from the ongoing Phase III BELLINI trial, a study in relapsed/refractory multiple myeloma, in which a higher proportion of deaths was observed in the venetoclax arm compared to the control arm of the trial. [AbbVie] Press Release

I-Mab Biopharma and MorphoSys Announce Initiation of Pivotal Phase II Study of TJ202/MOR202 for Multiple Myeloma

I-Mab Biopharma and MorphoSys AG announced that the first patient dosing has been achieved in a Phase II multi-center clinical study in Taiwan to evaluate an investigational human CD38 antibody TJ202/MOR202 in patients with relapsed or refractory multiple myeloma. TJ202/MOR202 is an antibody developed by MorphoSys AG. [I-Mab Biopharma (PR Newswire Association LLC.)] Press Release

Xynomic Pharma Achieves Important Regulatory Milestones in China and EU in Potentially Pivotal Kidney Cancer and Lymphoma Trials

The Independent Ethics Committee at the Cancer Hospital Chinese Academy of Medical Sciences in Beijing has approved Xynomic’s application to conduct two potentially pivotal Phase II trials, one to test abexinostat as a third-line mono therapy against diffuse large B-cell lymphoma and the other as a third-line mono therapy against follicular lymphoma. [Xynomic Pharma (PR Newswire Association LLC)] Press Release

European Commission Approves Roche’s Hemlibra for People with Severe Hemophilia a without Factor VIII Inhibitors

Roche announced that the European Commission has approved Hemlibra^® for routine prophylaxis of bleeding episodes in people with severe hemophilia A without factor VIII inhibitors. Hemlibra can be used in all age groups, and can also now be used at multiple dosing options for all indicated people with hemophilia A, including those with factor VIII inhibitors. [F. Hoffmann-La Roche Ltd] Press Release

Trump Proposes Slashing Science Spending at the NSF

US President Donald Trump has proposed cuts across the board at the National Science Foundation (NSF) in his 2020 budget request to Congress. The biggest decreases would hit funding for research in Antarctica and the Arctic, the geosciences, maths and physical sciences. [Nature News] Editorial

Norway Joins List of Countries Canceling Elsevier Contracts

Norway has become latest country to cancel its contracts with Elsevier following a dispute over access to research papers. In a statement published March 12, the Norwegian Directorate for ICT and Joint Services in Higher Education and Research, which represents a consortium of research institutions in the country, rejected Elsevier’s offer to lower some of its costs for Norwegian institutions because it didn’t go far enough to promote free access to published research. [The Scientist] Editorial

NEW 24^th Congress of the European Hematology Association (EHA)
June 13-16, 2019
Amsterdam, Netherlands

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

NEW Postdoctoral Fellowship – Hematopoiesis, Leukemia & Bone Marrow Failure Syndromes (The University of Texas Southwestern)

NEW Postdoctoral Scholarship – Murine Erythropoiesis (Lund University)

Postdoctoral Studies Scholarship – Stem Cells & Erythropoiesis in MDS (Karolinska Institutet)

Research Scientist – Leukemia Stem/Progenitor Cells (MD Anderson Cancer Center)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

Postdoctoral Scientist – Lymphocyte/Leukemia Research (City of Hope)

Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California, Davis)

Postdoctoral Position – RNA Modifications, Hematopoiesis & Cancer (Lund University)

Postdoctoral Research Fellow – Development of Lymphoid Cells (Lund University)

Faculty Positions – Hematology and Oncology (University of California, Davis)

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