Hematopoiesis News Volume 11.00 | Jan 7 2020

TOP STORY

Multipotent RAG1⁺ Progenitors Emerge Directly from Hemogenic Endothelium in Human Pluripotent Stem Cell-Derived Hematopoietic Organoids

Using RAG1:GFP human pluripotent stem cell reporter lines, scientists examined human T-cell genesis from pluripotent-stem-cell-derived hematopoietic organoids. Under conditions favoring T-cell development, RAG1⁺ cells progressively upregulated a cohort of recognized T-cell-associated genes, arresting development at the CD4⁺CD8⁺ stage. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

Erythromyeloid Progenitors Give Rise to a Population of Osteoclasts That Contribute to Bone Homeostasis and Repair

Researchers used lineage tracing studies-labeling cells expressing Cx3cr1, Csf1r or Flt3-to identify the precursors of osteoclasts in mice. They identified an erythromyeloid progenitor-derived osteoclast precursor population. [Nat Cell Biol] Abstract

CD93 Is Expressed on Chronic Myeloid Leukemia Stem Cells and Identifies a Quiescent Population Which Persists after Tyrosine Kinase Inhibitor Therapy

The authors demonstrated consistent and selective expression of CD93 on a lin^–CD34⁺CD38^–CD90⁺ chronic myeloid leukemia (CML) leukemic stem cell population and showed in vitro and in vivo data to suggest increased stem cell characteristics. [Leukemia] Abstract

In Vivo Single-Cell Lineage Tracing in Zebrafish Using High-Resolution Infrared Laser-Mediated Gene Induction Microscopy

Researchers traced the hematopoietic potential of hemogenic endothelium (HE) in the posterior blood island (PBI) of zebrafish embryos and found that HEs in the PBI were heterogeneous, which contained at least myeloid unipotent and myeloid-lymphoid bipotent subtypes. [eLife] Abstract

BCL-XL Expression Is Essential for Human Erythropoiesis and Engraftment of Hematopoietic Stem Cells

Scientists characterized the role of BCL-XL for survival and function of human hematopoietic cells, with the aim to predict hematological side effects of novel BCL-XL-inhibiting BH3-mimetics and to identify hematological malignancies potentially responsive to such inhibitors. [Cell Death Dis] Full Article

PML/RARa Interferes with NRF2 Transcriptional Activity Increasing the Sensitivity to Ascorbate of Acute Promyelocytic Leukemia Cells

Since researchers demonstrated how high doses of ascorbate preferentially killed leukemic blast cells from acute promyelocytic leukemia patients, they aimed to define the underlying mechanism and found that promyelocytic leukemia/retinoic acid receptor α (PML/RARa) inhibited NF-E2 p45-related factor 2 (NRF2) function, impeded its transfer to the nucleus and enhanced its degradation in the cytoplasm. [Cancers] Full Article | Graphical Abstract

A Regulatory Role for CHD2 in Myelopoiesis

Investigators used a CRISPR-Cas9 screening approach to identify new epigenetic regulators in myeloid differentiation. They designed a Chromatin-UMI CRISPR guide library targeting 1092 epigenetic regulators. [Epigenetics] Abstract

Origin of Monocytes/Macrophages Contributing to Chronic Inflammation in Chagas Disease: SIRT1 Inhibition of FAK-NFκB-Dependent Proliferation and Proinflammatory Activation of Macrophages

Flow cytometry studies showed an increase in maturation of bone marrow HSC-derived monocytes of proinflammatory and anti-inflammatory phenotype in acutely- and chronically-infected mice; however, these cells were not increased in splenic compartment of infected mice. [Cells] Full Article

CLINICAL RESEARCH

Single-Cell Analysis Based Dissection of Clonality in Myelofibrosis

Investigators showed the clonal evolution structure in 15 myelofibrosis patients while receiving treatment with JAK inhibitors. Whole-exome sequencing at multiple time points revealed acquisition of somatic mutations and copy number aberrations over time. [Nat Commun] Full Article

Detection of the KIT^D816V Mutation in Myelodysplastic and/or Myeloproliferative Neoplasms and Acute Myeloid Leukemia with Myelodysplasia-Related Changes Predicts Concurrent Systemic Mastocytosis

A review of clinical next-generation sequencing was performed at the authors’ institutions in patients with known or suspected hematologic malignancies over an eight-year period revealed 64 patients with both a pathogenic KIT mutation detected at one or more timepoints and available bone marrow biopsy materials. [Mod Pathol] Abstract

Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News.

The Leukemia Stem Cell: Similarities, Differences and Clinical Prospects in CML and AML

Investigators review many of the similarities and differences that exist between leukemia stem cells in chronic myeloid leukemia (CML) and acute (Archive)ML and examine the therapeutic strategies that could be used to eradicate them. [Nat Rev Cancer] Abstract

Dynamic Responses of the Hematopoietic Stem Cell Niche to Diverse Stresses

In this review, the authors focus on how bone marrow microenvironment components respond to different insults including inflammation, malignant hematopoiesis and chemotherapy. They highlight common and unique patterns among multiple cell types and their environment and discuss current limitations in our understanding of this complex and dynamic tissue. [Nat Cell Biol] Abstract

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

Trillium Therapeutics Provides Update on Its TTI-621 and TTI-622 CD47 Programs

Trillium Therapeutics, Inc. provided an update on its TTI-621 and TTI-622 clinical programs. “We have now completed the initial dose finding and signal seeking parts of our Phase I study of intravenous TTI-621 at doses up to 0.5 mg/kg,” said Dr. Jan Skvarka, President and Chief Executive Officer of Trillium. [Trillium Therapeutics, Inc.] Press Release

GlycoMimetics and Apollomics Announce Exclusive Collaboration and License Agreement to Develop and Commercialize Uproleselan and GMI-1687 in Greater China

GlycoMimetics, Inc. and Apollomics, Inc. announced an exclusive collaboration and license agreement for the development and commercialization of uproleselan and GMI-1687 in Mainland China, Hong Kong, Macau and Taiwan, also known as Greater China. [GlycoMimetics, Inc.] Press Release

A Year after the Midterm Elections, Where Are They Now?

November 2018 saw a wave of candidates from all walks of science – engineering, physics, medicine, and other life sciences – win first-time positions in the House, Senate, and state legislatures across the country. Of 20 STEM candidates running for Congressional seats that The Scientist counted last year, 10 won their races, the vast majority of them Democrats as well as political newcomers. [The Scientist] Editorial

UK Group Tackles Reproducibility in Research

Last month, ten UK universities became part of the UK Reproducibility Network, joining a network that already includes stakeholders such as the Academy of Medical Sciences, Research Libraries UK, the National Institute for Biological Standards and Control, journals including Nature and PLOS, and local networks of researchers. [The Scientist] Editorial

NEW Lorne Cancer Conference
February 13-15, 2020
Lorne, Australia

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

NEW Team Leader – Clonal Evolution in Leukemia (Institute of Cancer Research)

Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.)

Faculty Position – Cancer Epidemiology (MD Anderson Cancer Center)

Research Fellow – Hematology & Blood Disorders (New York Blood Center)

Postdoctoral Fellowships – Cancer Research (Harvard Medical School)

Postdoctoral Fellowship – Leukemia (Uniformed Services University of the Health Sciences)

Postdoctoral Fellow – Erythropoiesis (Mount Sinai School of Medicine)

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

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

Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Hematopoiesis News? Click here to submit!

Comments or suggestions? Submit your feedback here.