Hematopoiesis News Volume 8.18 | May 9 2017

TOP STORY

Vitamin A Deficiency Is Detrimental to Blood Stem Cells

Lack of vitamin A in the body has a detrimental effect on the hematopoietic system in the bone marrow. The deficiency causes a loss of important blood stem cells, scientists report. These are dormant stem cells that only become active in an emergency such as heavy blood loss or infection. These findings will contribute to better comprehending the maturation process of blood cells and also open up new prospects in cancer therapy. [Press release from the German Cancer Research Center (DKFZ) discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Wnt5a Induces ROR1 to Complex with HS1 to Enhance Migration of Chronic Lymphocytic Leukemia Cells

The authors found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly-isolated chronic lymphocytic leukemia (CLL) cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA, and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. [Leukemia] Abstract

RNA Editing Signature during Myeloid Leukemia Cell Differentiation

Investigators showed that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or VitaminD3/GM-CSF-driven differentiation, both ADAR1 and ADAR2 enzymes were up-regulated, with a concomitant global increase of A-to-I RNA editing. [Leukemia] Abstract

In Vivo Engineering of Bone Tissues with Hematopoietic Functions and Mixed Chimerism

The authors devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Their results showed that matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. [Proc Natl Acad Sci USA] Abstract | Press Release

A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre-Hematopoietic Stem Cells

Whether the full hematopoietic repertoire of embryonic hematopoietic stem cells (HSCs) initially includes unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. By combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, researchers analyzed emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. [Stem Cell Reports] Full Article

Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-Aortic Cluster Architecture

Using Fucci reporter mice that enable in vivo visualization of cell-cycle status, investigators detected increased proliferation during pre-hematopoietic stem cell (HSC) expansion followed by a slowing down of cycling once cells start to acquire a definitive HSC state, similar to fetal liver HSCs. They observed time-specific changes in intra-aortic hematopoietic clusters corresponding to HSC maturation stages. [Stem Cell Reports] Full Article | Graphical Abstract

CRISPR/Cas9 Mediated CCR5 Ablation in Human Hematopoietic Stem/Progenitor Cells Confers HIV-1 Resistance In Vivo

The authors established a CRISPR/Cas9 gene editing system in human CD34⁺ hematopoietic stem/progenitor cells (HSPCs) and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdc^scid/IL–2Rγ^null mice. The CCR5 disruption efficiency in their system remained robust in secondary transplanted repopulating hematopoietic cells. [Mol Ther] Abstract

Adiponectin Enhances Quiescence Exit of Murine Hematopoietic Stem Cells and Hematopoietic Recovery through mTORC1 Potentiation

Given that adipose tissue is an endocrine organ with pleiotropic functions, scientists hypothesized that adipocyte-derived factors, especially adiponectin, an anti-inflammatory adipokine involved in regulation of granulopoiesis, are implicated in hematopoietic stem cell activation. Myeloablative intervention increased bone marrow adiponectin by multiple mechanisms, including adipocyte expansion and increased diffusion from the blood. [Stem Cells] Abstract

Persistent Response of Fanconi Anemia Hematopoietic Stem and Progenitor Cells to Oxidative Stress

By employing an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, investigators showed that hematopoietic stem and progenitor cells (HSPCs) from mice deficient for the Fanconi anemia (FA) gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, they demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. [Cell Cycle] Abstract

CLINICAL RESEARCH

Partial Break in Tolerance of NKG2A⁻/LIR-1⁻ Single KIR⁺ NK Cells Early in the Course of HLA-Matched, KIR-Mismatched Hematopoietic Cell Transplantation

Natural killer (NK) cell subpopulations from eight HLA-matched but killer cell immunoglobulin-like receptor (KIR)/HLA-ligand-mismatched patient–donor pairs were analyzed in the course of allogeneic hematopoietic stem cell transplantation (HCT). The patients’ post-transplantation NKG2A⁻/LIR-1⁻ NK cells, which expressed only inhibitory KIRs for which the patient had no HLA class I ligands, showed higher cytotoxic capacity than the NKG2A⁻/LIR-1⁻ NK cells lacking any inhibitory KIRs that remained tolerant throughout the course of HCT. [Bone Marrow Transplant] Abstract

Population Pharmacokinetics of Fludarabine in Patients with Aplastic Anemia and Fanconi Anemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Researchers evaluated the population pharmacokinetics of fludarabine (F-araA) and its influence on hematopoietic stem cell transplantation (HSCT) outcome in patients with aplastic anemia and Fanconi anemia undergoing HSCT. Patients carrying a 5′-UTR polymorphism in NT5E gene exhibited significantly lower plasma F-araA clearance compared to those with wild-type genotype. [Bone Marrow Transplant] Full Article

From Genetic Single Candidate Gene Studies to Complex Genomics of GvHD

The authors summarize current knowledge on the effect of the donor and recipient genotypes on graft-versus-host disease (GvHD), starting from human leucocyte antigen (HLA) matching for an optimal donor selection, typing of non-classical HLA and minor histocompatibility antigens through the polymorphic variations in genes coding for non-HLA proteins contributing to the development of GvHD and response to treatment. [Br J Haematol] Abstract

Cardiotoxicity and Cardiomyopathy in Children and Young Adult Survivors of Hematopoietic Stem Cell Transplant

Scientists review the causes of cardiac injury, discuss strategies for detection of cardiomyopathy, and evaluate therapeutic options for long-term hematopoietic stem cell transplant survivors. [Pediatr Blood Cancer] Abstract

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

Syros Presents New Insights on Mechanism of Action of SY-1425, Its First-in-Class Selective RARα Agonist, in Oral Plenary Session

Syros Pharmaceuticals announced new preclinical data that further elucidates the mechanism of action of SY-1425, its oral first-in-class selective retinoic acid receptor alpha (RARα) agonist currently in a Phase II clinical trial in genomically defined subsets of patients with acute myeloid leukemia and myelodysplastic syndrome. [Press release from Syros Pharmaceuticals discussing research to be presented at the 2017 American Association for Cancer Research (AACR) Hematologic Malignancies: Translating Discoveries to Novel Therapies, Boston] Press Release

European Commission Approves KEYTRUDA^® (Pembrolizumab) for Patients with Relapsed or Refractory Classical Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant and Brentuximab Vedotin (BV), or Who Are Transplant-Ineligible and Have Failed BV

Merck announced that the European Commission has approved KEYTRUDA^®, the company’s anti-PD-1 therapy, for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant and BV, or who are transplant-ineligible and have failed BV. [Merck & Co., Inc.] Press Release

Rasna Therapeutics, Inc. Advances Development of a Novel Treatment for NPM1-Mutated Acute Myeloid Leukemia

Rasna Therapeutics, Inc. provided an update from further studies towards the development of formulated RASP-101, a novel modality for treatment of NPM1-mutated acute myeloid leukemia (AML). The Phase II clinical trial involved patients with refractory or relapsed NPM1-mutated AML. They were treated with cycles of dactinomycin. [Rasna Therapeutics, Inc. (Business Wire, Inc.)] Press Release

RYDAPT^® (Midostaurin) Approved for the Treatment of FLT3-Mutated Acute Myeloid Leukemia, Available for Order at Biologics, Inc.

Biologics, Inc. announced that it has been selected by Novartis to be in the distribution network for RYDAPT^®, a new oral treatment for adults with newly-diagnosed acute myeloid leukemia who are FLT3 mutation-positive. [Biologics, Inc.] Press Release

Biotech Execs, Academic Leaders Make Case for NIH Funding at White House Meeting

Could the Trump administration be changing its mind about slashing funding for the National Institutes of Health (NIH)? Scientific leaders were optimistic after meeting at the White House with several biotech executives to discuss the “ecosystem” in which federally funded basic research leads to discoveries that companies turn into treatments. [ScienceInsider] Editorial

Scientists Relieved by Emmanuel Macron’s French Election Victory

French scientists say they’re relieved and happy that their country’s next president will be Emmanuel Macron, a 39-year-old former civil servant and economy minister who swept to victory in elections. Macron intends to make cuts to public spending, but has said he will ring-fence the budgets for research and higher education, areas that he wants to make the central plank of a program to boost innovation and cut unemployment. [Nature News] Editorial

NEW 18^th International Congress of Developmental Biology
June 18-22, 2017
Singapore, Singapore

NEW 22^nd European Hematology Association Congress
June 22-25, 2017
Madrid, Spain

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

NEW Full Member Faculty – Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center)

NEW Senior Research Scientist – Hematopoietic Stem Cells (Texas Tech University Health Sciences Center El Paso)

Faculty Position – Normal and Malignant Hematopoiesis (Cincinnati Children’s Hospital)

Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel)

Postdoctoral Position – Acute Myeloid Leukemia (German Cancer Research Center)

Postdoctoral Position – Hematopoietic Stem/Progenitor Cell Research (Frederick National Laboratory for Cancer/National Cancer Institute)

Principal Investigator – Hematopoietic and Immune System (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Senior Research Associate – Hematopoietic and Immune System (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Postdoctoral Position – Leukemia Research (VIB-KU Leuven Center for Cancer Biology)

Scientist – Biological Function of Hematopoietic Stem Cells/Progenitors (HemoGenyx LLC)

Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

Postdoctoral Fellow – Changes in Hematopoietic Stem Cell Biology (Lund University)

Principal Scientist – Immuno Oncology (Celgene Corporation)

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

Associate Director – Translational Development (Celgene Corporation)

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.