Hematopoiesis News Volume 10.38 | Oct 1 2019

TOP STORY

Germline NPM1 Mutations Lead to Altered rRNA 2′-O-Methylation and Cause Dyskeratosis Congenita

Researchers demonstrated the importance of 2′-O-methylation-regulated translation for cellular growth, differentiation and HSC maintenance, and showed that Npm1 inactivation in adult HSC resulted in bone marrow failure. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

Muscarinic Acetylcholine Receptor Regulates Self-Renewal of Early Erythroid Progenitors

Scientists found that the muscarinic acetylcholine receptor, cholinergic receptor, muscarinic 4 (CHRM4), pathway regulated burst-forming unit erythroid self-renewal and that pharmacological inhibition of CHRM4 corrected anemias of myelodysplastic syndrome, aging, and hemolysis. [Sci Transl Med] Abstract | Press Release

Functional Characterization of BRCC3 Mutations in Acute Myeloid Leukemia with t(8;21)(q22;q22.1)

Inactivation of BRCA1/BRCA2-containing complex 3 (BRCC3) by CRISPR/Cas9 resulted in improved proliferation in t(8;21)(q22;q22.1) positive AML cell lines and together with expression of AML1-ETO induced unlimited self-renewal in mouse hematopoietic progenitor cells in vitro. [Leukemia] Full Article

Antibiotic Treatment Ameliorates Ten-Eleven Translocation 2 (TET2) Loss-of-Function Associated Hematological Malignancies

Investigators discovered that Tet2 depletion led to aberrant expansion of myeloid cells, which was correlated with elevated serum levels of pro-inflammatory cytokines at the pre-malignant stage. [Cancer Lett] Abstract

Isoform-Specific Involvement of Brpf1 in Expansion of Adult Hematopoietic Stem and Progenitor Cells

The authors performed a chemical screen using nine bromodomain inhibitors, and found that the bromodomain and PHD finger containing protein 1 (Brpf1) inhibitor OF-1 enhanced the expansion of Lin^–Sca-1⁺c-Kit⁺ hematopoietic stem and progenitor cells ex vivo without skewing their lineage differentiation potential. [J Mol Cell Biol] Full Article

HPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function

Researchers demonstrated that hematopoietic stem and progenitor cells (HSPCs) showed a strong dependence on hypoxanthine guanine phosphoribosyl transferase (HPRT)-associated purine salvaging. HSPCs with lower HPRT activity had a severely reduced competitive repopulation ability upon transplantation. [Stem Cells] Abstract

The Effects of Dietary Fatty Acids on Bone, Hematopoietic Marrow and Marrow Adipose Tissue in a Murine Model of Senile Osteoporosis

Feeding fish oil-enriched diet prevented age-related bone and hematopoietic bone marrow (HBM) loss, by reducing marrow adipose tissue (MAT) expansion. Results further emphasized the role(s) of MAT expansion in bone and HBM atrophy. [Aging (Albany NY)] Full Article

A Novel Mouse Model of Acute Graft-versus-Host Disease Based on Chemotherapy Conditioning and G-CSF Mobilized Graft

Scientists constructed an MHC major mismatched acute graft-versus-host disease mouse model based on busulfan/cyclophosphomide conditioning and human G-CSF mobilized splenocytes as graft. Allogeneic transplanted mice showed quick and profound donor engraftment. [Bone Marrow Transplant] Abstract

Modest and Non-Essential Roles of the Endocannabinoid System in Immature Hematopoiesis of Mice

Using two different CB2-deficient mouse models, investigators studied the role of the endocannabinoid system for immature hematopoiesis. Moreover, they utilized both models to assess the specificity of putative CB2 agonists. [Exp Hematol] Abstract

CLINICAL RESEARCH

CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia

Scientists transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells into a patient with human immunodeficiency virus (HIV) type 1 infection and acute lymphoblastic leukemia. [N Engl J Med] Abstract

Allogeneic Stem-Cell Transplantation with Sequential Conditioning in Adult Patients with Refractory or Relapsed Acute Lymphoblastic Leukemia: A Report from the EBMT Acute Leukemia Working Party

Researchers identified 115 patients with relapsed or primary-refractory acute lymphoblastic leukemia allografted from matched related, matched unrelated, or haploidentical donor. Median follow-up was 37 months. At day 100, cumulative incidences of grade II-IV/III-IV acute graft-versus-host-disease were 30% and 17%, respectively. [Bone Marrow Transplant] Abstract

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“Hierarchy” and “Holacracy”; A Paradigm of the Hematopoietic System

The authors propose a new paradigm of the hematopoietic system, in which individual HSCs are actively involved. [Cells] Full Article

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

Ziopharm Oncology Announces FDA Clearance of IND for Rapid Personalized Manufacture of CD19-Specific CAR-T

Ziopharm Oncology, Inc. announced that the FDA has cleared an investigational new drug application (IND) for a Phase I clinical trial to evaluate CD19-specific CAR-T, produced using a process termed rapid personalized manufacture, as an investigational treatment for patients with relapsed CD19⁺ leukemias and lymphomas. [Ziopharm Oncology, Inc.] Press Release

Geron Announces Fast Track Designation Granted to Imetelstat for Relapsed/Refractory Myelofibrosis

Geron Corporation announced that the FDA has granted Fast Track designation to imetelstat for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to janus kinase inhibitor treatment, or relapsed/refractory MF. [Geron Corporation] Press Release

Genmab Announces US FDA Approval of DARZALEX^® (Daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone for Frontline Multiple Myeloma

Genmab A/S announced that the FDA has approved the use of daratumumab in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant. [Genmab A/S] Press Release

FibroGen Announces Initiation of Phase II Clinical Trial of Roxadustat for the Treatment of Anemia in Cancer Patients Receiving Chemotherapy

FibroGen, Inc. announced first patient dosed in the company’s Phase II clinical study of roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, for the treatment of chemotherapy-induced anemia in cancer patients receiving chemotherapy. [FibroGen, Inc.] Press Release

India Pushes for Alternatives to Animals in Biomedical Research

India has become the latest nation to explore using emerging technologies such as organs-on-a-chip to replace animals in research. Earlier this month, the national regulator for biomedical research recommended fast-tracking investments in technologies that can replace animals. [Nature News] Editorial

Two-Thirds of Researchers Report ‘Pressure to Cite’ in Nature Poll

An online poll answered by more than 4,300 Nature readers suggests that most researchers have felt pressured by peer reviewers to cite studies in their papers that seem unnecessary. [Nature News] Editorial

NEW Precision Health: Molecular Basis, Technology and Digital Health
November 13-16, 2019
Heidelberg, Germany

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

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

NEW Postdoctoral Fellowship – Hematopoietic Cell Transplantation (University of Maryland)

NEW Chair – Inflammation and Hematopoiesis (Technische Universität Dresden)

Postdoctoral Scholar – Hematopoietic Cells (Penn State University)

Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer)

Visiting Research Specialist – Hematopoietic Stem Cells (University of Illinois)

Faculty – Hematopoietic Biology and Malignancy (MD Anderson Cancer Center)

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

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

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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