Hematopoiesis News Volume 8.06 | Feb 14 2017

TOP STORY

Metabolic Gatekeeper Function of B-Lymphoid Transcription Factors

By combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, the authors identified a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Their metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

The Creatine Kinase Pathway Is a Metabolic Vulnerability in EVI1-Positive Acute Myeloid Leukemia

Through transcriptomic and metabolomic profiling of hematopoietic cells, scientists revealed that EVI1 overexpression alters cellular metabolism. A screen using pooled short hairpin RNAs identified the ATP-buffering, mitochondrial creatine kinase CKMT1 as necessary for survival of EVI1-expressing cells in subjects with EVI1-positive acute myeloid leukemia. [Nat Med] Abstract

Cholinergic Signals from the CNS Regulate G-CSF-Mediated HSC Mobilization from Bone Marrow via a Glucocorticoid Signaling Relay

The authors showed that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes granulocyte colony-stimulating factor (G-CSF)-elicited hematopoietic stem cells (HSCs) mobilization via hormonal priming of the hypothalamic-pituitary-adrenal axis. Blockade of Chrm1 in the CNS, but not the periphery, reduces HSC mobilization. [Cell Stem Cell] Abstract | Graphical Abstract

Drug Discovery for Diamond-Blackfan Anemia Using Reprogrammed Hematopoietic Progenitors

Identifying therapeutics for diamond-blackfan anemia (DBA) requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, researchers adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. [Sci Transl Med] Abstract | Press Release

AMKL Chimeric Transcription Factors Are Potent Inducers of Leukemia

Scientists demonstrated that the introduction of GATA2-HOXA9, MN1-FLI1 or NIPBL-HOXB9 into murine bone marrow induces overt disease in syngeneic transplant models. With the exception of MN1, full penetrance was not achieved through the introduction of fusion partner genes alone, suggesting that the chimeric transcripts possess a unique gain of function phenotype. [Leukemia] Abstract

Inhibition of Serotonin Receptor Type 1 in Acute Myeloid Leukemia Impairs Leukemia Stem-Cell Functionality: A Promising Novel Therapeutic Target

Acute myeloid leukemia (AML) cells differentially expressed serotonin receptors type 1 (HTR1) compared to healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome. Inhibition of HTR1s activated the apoptosis program, induced differentiation and reduced the clonogenic capacity, while minimal effect was observed on healthy blood cells. [Leukemia] Abstract

EVI2B Is a C/EBPα Target Gene Required for Granulocytic Differentiation and Functionality of Hematopoietic Progenitors

The authors identified the Ecotropic Viral Integration Site 2B (EVI2B) gene as a direct target of CCAAT/enhancer binding protein alpha (C/EBPα). They showed that the product of the gene, the transmembrane glycoprotein EVI2B, is abundantly expressed on the surface of primary hematopoietic cells, the highest levels of expression being reached in mature granulocytes. [Cell Death Differ] Abstract

Macrophages Confer Survival Signals via CCR1-Dependent Translational MCL-1 Induction in Chronic Lymphocytic Leukemia

Investigators established that macrophages (Mφs) induced survival because of an exclusive upregulation of myeloid leukemia cell differentiation protein 1 (MCL-1). Next, they investigated the mechanism underlying MCL-1 induction by Mφs in comparison with CD40L. [Oncogene] Full Article

Flow Dynamics and HSPC Homing in Bone Marrow Microvessels

The authors developed two complementary intravital two-photon imaging approaches to determine blood flow dynamics and velocities in multiple vessel segments by capturing the motion of red blood cells. High-resolution spatiotemporal measurements through a cranial window to determine short-time dynamics of flowing blood cells and repetitive centerline scans were used to obtain a detailed flow-profile map with hemodynamic parameters. [Cell Rep] Full Article | Graphical Abstract

Connexin30.3 Is Expressed in Mouse Embryonic Stem Cells and Is Responsive to Leukemia Inhibitory Factor

Connexin (Cx) 30.3 was pluripotent state-specific and upregulated by leukemia inhibitory factor, a specific cytokine that maintains the pluripotent state of embryonic stem cell, via a Jak signaling pathway. Cx30.3 protein was localized to both the cell membrane and cytosol. [Sci Rep] Full Article

Mechanisms Responsible for the Synergistic Antileukemic Interactions between ATR Inhibition and Cytarabine in Acute Myeloid Leukemia Cells

Scientists investigated the antileukemic effects of ATR inhibition alone or combined with cytarabine in acute myeloid leukemia (AML) cells. Treatment with the ATR-selective inhibitor AZ20 caused proliferation inhibition in AML cell lines and primary patient samples. [Sci Rep] Full Article

CLINICAL RESEARCH

The Dynamics of RUNX1-RUNX1T1 Transcript Levels after Allogeneic Hematopoietic Stem Cell Transplantation Predict Relapse in Patients with T(8;21) Acute Myeloid Leukemia

RUNX1-RUNX1T1 transcript levels were measured in bone marrow samples collected from 208 patients at scheduled time points after transplantation. [J Hematol Oncol] Full Article

Patient Age and Number of Apheresis Days May Predict Development of Secondary Myelodysplastic Syndrome and Acute Myelogenous Leukemia after High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Lymphoma

The authors’ primary goal was to analyze the association between the number of apheresis days needed to collect the requisite stem cell dose in addition to the previously described factors such as age, sex, number and type of prior chemotherapeutic regimens, disease type and status, and the risk of developing secondary myelodysplastic syndrome or acute myelogenous leukemia. [Transfusion] Abstract

MLL₅ (KMT₂E): Structure, Function, and Clinical Relevance

The authors summarize recent research characterizing the structural features and biological roles of mixed lineage leukemia (MLL)₅, and they highlight the potential implications of MLL₅ dysfunction in human disease. [Cell Mol Life Sci] Abstract

The Evolving View of the Hematopoietic Stem Cell Niche

Hematopoietic stem cells (HSC) reside in specialized microenvironments known as niches. The niche is essential to support HSC function and to maintain a correct balance between self-renewal and differentiation. Recent advances in defining different mesenchymal and endothelial bone marrow cell populations as well as hematopoietic stem and progenitor cells greatly enhanced the understanding of these niches and of the molecular mechanisms by which they regulate HSC function. [Exp Hematol] Abstract

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

Amgen Submits Supplemental Biologics License Application for BLINCYTO^® (Blinatumomab) in Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

Amgen announced the submission of a supplemental Biologics License Application to the U.S. Food and Drug Administration for BLINCYTO^® to include overall survival data from the Phase III TOWER study, supporting the conversion of BLINCYTO’s accelerated approval to full approval. The sBLA also includes new data supporting the treatment of patients with Philadelphia chromosome-positive relapsed or refractory B-cell precursor acute lymphoblastic leukemia. [Amgen] Press Release

Cancer Research UK Announces Inaugural Grand Challenge Teams to Answer the Biggest Questions in Cancer

Cancer Research UK announces that four international teams are the first recipients of its global £100 million Grand Challenge competition, which aims to overcome the biggest challenges facing cancer researchers in a global effort to beat cancer sooner. [Cancer Research UK] Press Release

With Stringent Oversight, Heritable Germline Editing Clinical Trials Could One Day Be Permitted for Serious Conditions; Non-Heritable Clinical Trials Should Be Limited to Treating or Preventing Disease or Disability at This Time

Clinical trials for genome editing of the human germline – adding, removing, or replacing DNA base pairs in gametes or early embryos – could be permitted in the future, but only for serious conditions under stringent oversight, says a new report from the National Academy of Sciences and the National Academy of Medicine. [National Academies of Sciences, Engineering, and Medicine] Editorial

German Scientists Regain Access to Elsevier Journals

A stand-off in which dozens of German universities declined to pay for access to journals from publishing giant Elsevier has been partially resolved. [Nature News] Editorial

Debate Erupts over Plan to Create Another Online Destination for Biology Preprints

A plan to create a new repository for biomedical and biology preprints has earned the endorsement of nearly a dozen major science funders, including government agencies, major foundations, and research charities. But it also has sparked a debate about whether an existing preprint repository, bioRxiv.org, should be the natural home for such material. [ScienceInsider] Editorial

Lawsuit Aims to Force USDA to Repost Scrubbed Animal Welfare Records

Put the records back on the internet. That’s the demand made in a lawsuit filed against the U.S. Department of Agriculture (USDA) by an animal law expert at Harvard University, together with the People for the Ethical Treatment of Animals and several other animal welfare groups. The plaintiffs allege that USDA violated the federal Freedom of Information Act when it removed thousands of animal welfare inspection reports and other records from a publicly accessible website. [ScienceInsider] Editorial

NEW Tumor Metabolism: Mechanisms and Targets
March 5-9, 2017
Whistler, Canada

NEW Adaptations to Hypoxia in Physiology and Disease
March 5-9, 2017
Whistler, Canada

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

NEW Postdoctoral Fellow – Leukemia Lymphoma (Emory University)

NEW Postdoctoral Fellow – Human Genome Editing (Johns Hopkins University School of Medicine)

NEW Principal Scientist – Translational Development, Myeloid Disease Strategy (Celgene Corporation)

NEW Scientist – Primary Cells (STEMCELL Technologies, Inc.)

Senior Scientist – Translational and Diagnostic Informatics (Celgene Corporation)

Postdoctoral Fellow – Hematopoietic Gene Regulation and Leukemia (Boston Children’s Hospital and Harvard Medical School)

Postdoctoral Researcher – Genetic Alterations Involved in the Development, Maintenance and Relapse of Acute Leukemia (University of Basel)

Scientist – Regulatory Support (Cook MyoSite, Inc.)

Postdoctoral Position – Leukemia Research (Department of Biomedicine, University Hospital Basel)

Postdoctoral Fellow – Age Associated Changes of the Hematopoietic Stem Cell Compartment (National Institutes of Health / National Institute on Aging)

Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame)

Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute)

Principal Scientist – Translational Development (Celgene Corporation)

Associate Director – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC)

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.