Hematopoiesis News Volume 7.48 | Dec 6 2016

TOP STORY

Self-Renewal of a Purified Tie2⁺ Hematopoietic Stem Cell Population Relies on Mitochondrial Clearance

Scientists demonstrated, by characterizing at the single-cell level a purified and minimally heterogeneous murine Tie2⁺ hematopoietic stem cell (HSC) population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality control process in mitochondria, plays an essential role in self-renewing expansion of Tie2⁺ HSCs. [Science] Abstract

(Ranked by impact factor of the journal)

Depleting Dietary Valine Permits Nonmyeloablative Mouse Hematopoietic Stem Cell Transplantation

Investigators report that the essential amino acid valine is indispensable for the proliferation and maintenance of hematopoietic stem cell (HSC). Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. [Science] Abstract

Dickkopf-1 Promotes Hematopoietic Regeneration via Direct and Niche-Mediated Mechanisms

Scientists showed that deletion of the pro-apoptotic genes Bak and Bax in osterix-expressing cells in mice promotes hematopoietic stem cell regeneration and hematopoietic radioprotection following total body irradiation. [Nat Med] Abstract | Press Release

Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia

To isolate and characterize relapse-inducing cells, researchers used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia. They identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. [Cancer Cell] Full Article | Graphical Abstract

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis

The authors showed that MED12, a member of the Mediator kinase module, is an essential regulator of hematopoietic stem cell (HSC) homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality. [Cell Stem Cell] Abstract | Graphical Abstract

Cirmtuzumab Inhibits Wnt5a-Induced Rac1-Activation in Chronic Lymphocytic Leukemia Treated with Ibrutinib

Scientists found that chronic lymphocytic leukemia (CLL) cells of patients treated with ibrutinib had activated Rac1. Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting Bruton’s tyrosine kinase and B cell receptor-signaling. [Leukemia] Full Article

EphA3 as a Target for Antibody Immunotherapy in Acute Lymphoblastic Leukemia

Researchers showed that the therapeutic effect of the anti-EphA3 antibody was greatly enhanced by adding an alpha particle-emitting ²¹³Bismuth payload. [Leukemia] Full Article

Outside-In Integrin Signaling Regulates Hematopoietic Stem Cell Function via Periostin-Itgav Axis

Investigators demonstrated that Periostin (Postn) via interaction with Integrin-αv (Itgav) regulates hematopoietic stem cell (HSC) proliferation. Systemic deletion of Postn results in peripheral blood anemia, myelomonocytosis and lymphopenia, while the number of phenotypic HSCs increases in the bone marrow. [Nat Commun] Full Article

Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration

The authors showed that growth factor receptor-bound protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10^m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10^+/+ mice. [Cell Rep] Full Article | Press Release | Graphical Abstract

Combined Nifuroxazide and SAT05f Therapy Reduces Graft-Versus-Host Disease after Experimental Allogeneic Bone Marrow Transplantation

Results showed combined therapy significantly decreased the severity of acute graft-versus-host disease and prolonged the survival rate. Furthermore, after treatment, the activation of CD4⁺ effect T cells was reduced, whereas Treg cells was increased, and the cytokine release was inhibited. [Cell Death Dis] Full Article

Impaired Hematopoietic Stem Cell Differentiation and Enhanced Skewing towards Myeloid Progenitors in Aged Caspase-2-Deficient Mice

Using young and aged Casp2^−/− mice, the authors demonstrated that deficiency of caspase-2 results in enhanced aneuploidy and DNA damage in bone marrow cells with ageing. [Cell Death Dis] Full Article

Low-Level Light Treatment Ameliorates Immune Thrombocytopenia

Researchers reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 minutes a day for a few consecutive days by near infrared light transmitted by an array of light-emitting diodes. LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive immune thrombocytopenia models induced by anti-CD41 antibody. [Sci Rep] Full Article

CLINICAL RESEARCH

Autologous Stem Cell Transplantation for Adult Acute Myelocytic Leukemia in First Remission-Better Outcomes after Busulfan and Melphalan Compared wth Busulfan and Cyclophosphamide: A Retrospective Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Autologous stem cell transplantation for adult acute myelogenous leukemia is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan with combined busulfan and cyclophosphamide before transplantation. [Cancer] Abstract

The Myeloma Stem Cell Concept, Revisited: From Phenomenology to Operational Terms

The authors summarize the current documentation and propose single-cell in vitro studies for future translational studies. By the classical approach, a CD19⁻/CD45^low/−/CD38^high/CD138⁺ malignant plasma cell, but not the CD19⁺/CD38^low/− memory B cell compartment, is enriched for tumorigenic cells that initiate myeloma in xenografted immunodeficient mice, supporting that myeloma stem cells are present in the malignant PC compartment. [Haematologica] Full Article

The Role of the Proteasome in AML

Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. [Blood Cancer J] Full Article

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

Late-Breaking Ibrutinib (IMBRUVICA^®) Data Show Complete or Partial Response in Two-Thirds of Patients with Chronic Graft-Versus-Host-Disease, a Frequent and Potentially Life-Threatening Complication of Stem Cell Transplant

AbbVie announced positive results from a Phase II study evaluating ibrutinib in patients with chronic graft-versus-host-disease, a serious and debilitating potential consequence of stem cell or bone marrow transplant, who failed prior systemic therapy. The study found ibrutinib demonstrated efficacy, sustained responses and reduced symptom severity, with an overall response rate of 67%. [Press release from AbbVie discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

BioLineRx Presents Positive Phase IIa AML Study and Mechanism-of-Action Data for BL-8040 Oncology Platform

BioLineRx Ltd. presented positive Phase IIa correlative data, as well as detailed mechanism-of-action data, for BL-8040, the company’s leading oncology platform. [Press release from BioLineRx Ltd. discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Novartis Data Shows Treatment-Free Remission Rates are Consistently above 50% Regardless of Reason for Switch to Tasigna^® from Glivec^®

Novartis announced new data from the Tasigna^® (nilotinib) ENESTop Treatment-free Remission (TFR) study, which demonstrate that TFR rates are consistent among Philadelphia chromosome-positive chronic myeloid leukemia patients who switched from Glivec^® (imatinib) due to intolerance, resistance or physician preference. [Press release from Novartis discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Late-Breaking Phase II Ibrutinib Study in Chronic Graft-Versus-Host-Disease (cGVHD) Showed Complete or Partial Response in up to Two-Thirds of Steroid Dependent or Refractory Patients

Janssen Research & Development, LLC. announced Phase II ibrutinib (IMBRUVICA^®) data showing encouraging results in patients with cGVHD, a life-threatening consequence of stem cell or bone marrow transplant, who failed prior systemic therapy. Study findings indicate ibrutinib demonstrated clinically meaningful and durable responses and reduced symptom severity, with an overall response rate of 67% in patients with cGVHD. [Press release from Janssen Research & Development, LLC. discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Gamida Cell Presents Positive Data from Phase I/II Study of NiCord^® as a Curative Treatment for Sickle Cell Disease

Gamida Cell announced results from its Phase I/II study of NiCord for sickle cell disease (SCD). The results presented at ASH demonstrated the potential of NiCord as a novel transplant approach for patients with SCD. The study provided a clinical proof of concept that NiCord, which was transplanted with an un-manipulated unit of umbilical cord blood, may enable very rapid engraftment in SCD patients transplanted after myeloablative conditioning. [Press release from Gamida Cell discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

PERSIST-2 Phase III Study of Pacritinib versus Best Available Therapy Shows Encouraging Clinical Activity in High-Risk Patients with Advanced Myelofibrosis in Late-Breaking Session

CTI BioPharma Corp. announced data from PERSIST-2, a randomized Phase III clinical trial comparing pacritinib with physician-specified best available therapy (BAT), for the treatment of high risk, thrombocytopenic myelofibrosis patients in a late-breaking oral session. Data presented at ASH showed that in myelofibrosis patients a statistically significant response rate in spleen volume reduction with pacritinib therapy was observed compared to BAT that included use of the approved JAK1/JAK2 inhibitor ruxolitinib. [Press release from CTI BioPharma Corp. discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

John Theurer Cancer Center Presents Groundbreaking Studies in Blood Cancer

The John Theurer Cancer Center announced highlights of their data presentations that include two late-breaking abstracts, 19 oral sessions and 27 poster discussions. Seventeen physicians from the John Theurer Cancer Center will be presenting data at ASH. [Press release from The John Theurer Cancer Center at Hackensack University Medical Center discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Blueprint Medicines Announces Proof-of-Concept Data from Phase I Clinical Trial of BLU-285 in Patients with Advanced Systemic Mastocytosis

Blueprint Medicines Corporation announced data from its ongoing Phase I trial evaluating BLU-285, an investigational medicine for the treatment of patients with advanced systemic mastocytosis. Blueprint Medicines is developing BLU-285 as a potent, highly selective inhibitor of D816V mutant KIT. [Press release from Blueprint Medicines Corporation discussing research presented at 58^th American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

AbbVie and Johns Hopkins to Collaborate on Cancer Research

AbbVie and the Johns Hopkins University School of Medicine announced that they signed a five-year collaboration agreement with the goal of advancing medical oncology research and discovery at both organizations. [AbbVie] Press Release

CASI Pharmaceuticals’ Import Drug Registration Application For EVOMELA^® Accepted for Review by CFDA

CASI Pharmaceuticals, Inc. announced that China’s Food and Drug Administration (CFDA) has accepted for review the company’s import drug registration application for EVOMELA^® (melphalan) for injection. [CASI Pharmaceuticals, Inc.] Press Release

Help Wanted: Canada Begins Search for Chief Science Adviser

Canada has officially launched its search for a chief government science adviser, fulfilling a campaign promise by Prime Minister Justin Trudeau. Science Minister Kirsty Duncan announced the move on 5 December, after spending the past year consulting scientists about the exact role that such an adviser should have. [Nature News] Editorial

Congress Is Poised to Back NSF’s Approach to Research

Congress has reached a truce—and possibly a lasting settlement—in the fiercely partisan three-year war between Republican leaders in the House of Representatives and the scientific community over how the National Science Foundation (NSF) should operate. The terms of the agreement, between House and Senate negotiators, may seem like minor changes. But the compromise, which the Senate could adopt as early as this week, resolves differences over how NSF should conduct peer review and manage research in ways that the agency thinks it can live with. [ScienceInsider] Editorial

Maryland Congressman in Running to Head NIH?

Representative Andy Harris (R–MD), an anesthesiologist who has shown a keen interest in the National Institutes of Health (NIH) while in Congress, has put his hat in the ring for NIH director in the incoming administration of President-elect Donald Trump, he told ScienceInsider. Harris says he knows that some biomedical scientists would view him as a controversial choice, but argues that his blend of research and political experience would make him a good advocate for addressing NIH’s flaws and for growing the agency’s budget in a time of fiscal restraint. [ScienceInsider] Editorial

NEW Keystone Symposium: Hematopoiesis
January 31-February 4, 2017
Banff, Canada

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

NEW Postdoctoral Fellowship – Pharmaceutics/Cancer Biology (Ohio State University)

Research Technologist – Hematopoietic Product Development (STEMCELL Technologies)

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)

Postdoctoral Fellowship – Stem Cell and Red Cell Biology (Lund University)

Postdoctoral Fellow(s) – Various Projects (Cincinnati Children’s Hospital Medical Center)

Research Associate – Hematology (Editas Medicine)

Postdoctoral Position – Hematology and Gene Therapy (Cincinnati Children’s Research Foundation)

Postdoctoral Position – Leukemia and Marrow Failure (H. Leighton Grimes)

Postdoctoral Position – Experimental Hematology and Cancer Biology (Cincinnati Children’s Research Foundation)

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.