Hematopoiesis News Volume 9.18 | May 8 2018

TOP STORY

Adrenergic Nerve Degeneration in Bone Marrow Drives Aging of the Hematopoietic Stem Cell Niche

Researchers showed that HSC aging critically depends on bone marrow innervation by the sympathetic nervous system (SNS), as loss of SNS nerves or adrenoreceptor β3 signaling in the bone marrow microenvironment of young mice led to premature HSC aging, as evidenced by appearance of HSC phenotypes reminiscent of physiological aging. [Nat Med] Abstract

(Ranked by impact factor of the journal)

CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease

Lentivirus vectors were used to deliver Cas9 and guide RNA to introduce inactivating mutations in ten-eleven translocation-2 (Tet2) and DNA (Cytosine-5)-methyltransferase 3a (Dnmt3a) in lineage-negative bone marrow cells. Following implantation into lethally-irradiated mice, these cells were engrafted and gave rise to labeled blood cell progeny. [Circ Res] Abstract

New Therapeutic Opportunities from Dissecting the Pre-B Leukemia Bone Marrow Microenvironment

Scientists focused on the development of precursor-B (pre-B) cell acute lymphoblastic leukemia in an immunocompetent BCR-ABL1⁺ model. They showed that hematopoiesis was perturbed, B lymphopoiesis was impaired, collagen production was reduced, and the number of osteoblastic cells was decreased in the bone marrow microenvironment. [Leukemia] Full Article

miR142 Loss-of-Function Mutations Derepress ASH1L to Increase HOXA Gene Expression and Promote Leukemogenesis

The authors showed that mutations associated with AML result both in loss of miR-142-3p function and in decreased miR-142-5p expression. miR142 loss altered the hematopoietic differentiation of multipotent hematopoietic progenitors, enhancing their myeloid potential while suppressing their lymphoid potential. [Cancer Res] Abstract

Identifying MicroRNA Determinants of Human Myelopoiesis

Investigators characterized the miRNA profile of human CD34⁺CD38⁺ myeloid progenitor cells, and mature monocytes and granulocytes isolated from cord blood using TaqMan Low Density Arrays. They identified 19 miRNAs that increased in both cell types relative to the common myeloid progenitor and 27 that decreased. [Sci Rep] Full Article

Different Effects of Granulocyte Colony-Stimulating Factor and Erythropoietin on Erythropoiesis

Researchers demonstrated that the effects of granulocyte colony-stimulating factor (G-CSF) on erythropoiesis and erythrocytic mobilization were independent of erythropoietin (EPO) secretion and, in contrast to EPO, G-CSF promoted progression of erythropoiesis through transition of early stage R2 (basophilic erythroblasts) to late stage R4 (orthochromatophilic erythroblasts). [Stem Cell Res Ther] Full Article

A Subset of Mobilized Human Hematopoietic Stem Cells Express Germ Layer Lineage Genes Which Can Be Modulated by Culture Conditions

Scientists were able to culture CD34⁺ cells expressing embryonic stem cell and embryonic germ layer lineage genes from adult human peripheral blood after standard mobilization procedures and from mouse peripheral blood. [Stem Cell Res Ther] Full Article

Calcium-Infiltrated Biphasic Hydroxyapatite Scaffolds for Human Hematopoietic Stem Cell Culture

Primary human hematopoietic stem cells and osteoblasts were co-cultured for six weeks. Cells were analyzed for surface markers by flow cytometry, metabolic activity, and hematopoietic multilineage differentiation potential. [Tissue Eng Part A] Abstract

Mtf2-PRC2 Control of Canonical Wnt Signaling Is Required for Definitive Erythropoiesis

The authors demonstrated a role for the classical polycomb repressive complex 2 (PRC2) accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. Mtf2^−/− erythroid progenitors demonstrated markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions. [Cell Discov] Full Article

CLINICAL RESEARCH

Phase I Trial of Plerixafor Combined with Decitabine in Newly Diagnosed Older Patients with Acute Myeloid Leukemia

Scientists investigated the safety and efficacy of decitabine combined with the CXCR4 antagonist plerixafor in newly diagnosed older patients with acute myeloid leukemia and evaluated the effects of plerixafor on leukemia stem cells. [Haematologica] Full Article

Blood Development: Hematopoietic Stem Cell Dependence and Independence

The authors review the current knowledge on HSC-dependent cell lineages and HSC-independent tissue-resident hematopoietic cells and how they arise during embryonic development. Classical embryological and genetic experiments, cell fate tracing data, single-cell imaging, and transcriptomics studies provide information on the molecular/cell trajectories that form the complete hematopoietic system. [Cell Stem Cell] Abstract

Causes and Consequences of Hematopoietic Stem Cell Heterogeneity

Researchers review the most recent findings regarding the causes and consequences of HSC heterogeneity, discuss their far-reaching implications, and suggest that so-called continuum-based models may help consolidate apparently divergent experimental observations in this field. [Cell Stem Cell] Abstract

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

St. Jude Children’s Research Hospital to Receive $1 Million Legacy Grant from The Links Foundation

St. Jude Children’s Research Hospital will receive the $1 million Legacy Grant that will help advance three sickle cell disease programs from The Links Foundation, Incorporated, the philanthropic arm of The Links, Incorporated, one of the nation’s oldest and largest African-American women’s volunteer service organizations. [St. Jude Children’s Research Hospital (PR Newswire Association LLC.)] Press Release

Janssen Announces DARZALEX^® (Daratumumab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma Who Are Transplant Ineligible

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the FDA has approved DARZALEX^® in combination with VELCADE^®, a proteasome inhibitor; melphalan, an alkylating agent; and prednisone – VMP – for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. [Janssen Global Services, LLC.] Press Release

Cellectis Files IND for UCART22 in Acute Lymphoblastic Leukemia (B-ALL)

Cellectis announced that the company has submitted an Investigational New Drug (IND) application to the FDA requesting approval to initiate a Phase I clinical trial for UCART22, Cellectis’ second wholly controlled TALEN^® gene-edited product candidate, for the treatment of B-ALL in adult patients. [Cellectis SA] Press Release

Daiichi Sankyo Announces Single Agent Quizartinib Significantly Prolongs Overall Survival Compared with Chemotherapy in Patients with Relapsed/Refractory AML with FLT3-ITD Mutations (QuANTUM-R Study)

Daiichi Sankyo Company, Limited announced that the pivotal QuANTUM-R Phase III study of single agent quizartinib met its primary endpoint of significantly prolonging overall survival compared to salvage chemotherapy in patients with relapsed/refractory acute myeloid leukemia (AML) with FLT3-ITD mutations after first-line treatment with or without hematopoietic stem cell transplantation. [Daiichi Sankyo Company, Ltd.] Press Release

Postdoc Hopes Pennsylvania Voters Will Help Her Re-Engineer How to Run for Congress

A postdoctoral researcher at the University of Pennsylvania who designs proteins for possible use in treating cancer, Sheehan has ignored conventional wisdom about the importance of raising tons of money to spread her message that she’s “a mother, a bioengineer, [and a] proud progressive.” Instead, she’s urging scientists and others in the community to offer their considerable skills to work for candidates they support. [ScienceInsider] Editorial

Basic Scientists Still Feel Pinch of New NIH Clinical Trial Policy

Basic researchers who study the brain and human behavior thought lawmakers had come to their rescue in March by blocking the National Institutes of Health (NIH) from redefining their studies as clinical trials. But NIH officials are still pushing ahead with new requirements that scientists say make no sense and will cripple their research. [ScienceInsider] Editorial

Petition Asks National Academy of Sciences to Boot Sexual Harassers

An online petition calling on the National Academy of Sciences to revoke memberships bestowed on people sanctioned for sexual harassment has garnered more than 250 signatures since it was posted on May 1. [The Scientist] Editorial

NEW 26^th European Orthopaedic Research Society (EORS) 2018
September 25-28, 2018
Galway, Ireland

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

NEW Cancer Researchers – Hematologic Malignancy (Cedars-Sinai Medical Center)

NEW Postdoctoral Fellow – Hematopoiesis and Leukemia (University of Pennsylvania)

NEW Postdoctoral Fellow – Hematopoiesis (University of Wisconsin)

NEW Group Leader – Leukemia Research (Hospital del Mar Research Institute)

Postdoctoral Position – Leukemia Research (Oslo Universitetssykehus HF)

Postdoctoral Fellow – B-Cell Lymphoma (University of Texas Health Science Center at San Antonio)

Postdoctoral Position – Stem Cell and Cancer Research (Institute for Research in Biomedicine)

Postdoctoral Position – Regulation of Normal and Malignant Hematopoiesis (Karolinska Institutet)

Postdoctoral Researchers – Plasticity of Myeloid Cells (BioMed X Innovation Center)

Postdoctoral Associate – Leukemia (St. Jude Children’s Research Hospital)

Tenure Track Faculty Position – Hematopathology (University of Virginia)

Postdoctoral Associate – Stem Cell Biology and Cancer Epigenetics (The Jackson Laboratory)

Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine)

Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia)

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