Volume 4.18 | May 14

Hematopoiesis News 4.18 May 14, 2013
Hematopoiesis News
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TOP STORY
Discovery Pinpoints Cause of Two Types of Leukemia, Providing Insights into New Treatment Approach
Researchers isolated the molecular mutation that causes chronic neutrophilic leukemia and atypical chronic myeloid leukemia in some patients. That mutation, occurring in a gene called colony stimulating factor 3 receptor (CSF3R), initiates a chain reaction involving other gene families known as SRC, JAK, and TNK2, which subsequently drives these diseases. The study results suggest that these patients could be helped by existing FDA-approved drugs designed to inhibit the chain reactions impacting JAK and SRC/TNK2, though clinical trials are needed. [Press release from Oregon Health & Science University discussing online prepublication in The New England Journal of Medicine] Press Release | Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

LABORATORY RESEARCH

EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation
Researchers found that EZH2 deletion or pharmacologic inhibition suppresses germinal center (GC) formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B cell differentiation. GC B cell-type diffuse large B cell lymphomas (DLBCLs) are mostly addicted to EZH2 but not the more differentiated activated B cell-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting. [Cancer Cell]
Abstract | Press Release

Deletion of the NF-κB Subunit p65/RelA in the Hematopoietic Compartment Leads to Defects in Hematopoietic Stem Cell Function
To investigate the role of the NF-κB subunit RelA/p65 in the regulation of hematopoietic stem cells (HSCs) in vivo, researchers generated mice lacking RelA/p65 in the hematopoietic compartment. Using this model system, they showed that loss of p65 severely impairs HSC function, and occurs in conjunction with increased HSPC cycling, extramedullary hematopoiesis, and differentiation defects. [Blood] Abstract

Concordant Mast Cell and Basophil Production by Individual Hematopoietic Blast Colony-Forming Cells
Previous studies have shown that mouse bone marrow cells can produce mast cells when stimulated in vitro by stem cell factor and interleukin-3. Experiments to define the marrow cells able to generate mast cells showed that the most active subpopulations were the Kit+ Sca1 progenitor cell fraction and the more ancestral Kit+ Sca1+ blast colony-forming cell fraction. [Proc Natl Acad Sci USA] Abstract

PAD4 Regulates Proliferation of Multipotent Hematopoietic Cells by Controlling c-myc Expression
Scientists showed that peptidylarginine deiminase 4 (PAD4), which is highly expressed in lineage Sca-1+ c-Kit+ cells of mouse bone marrow compared with other progenitor cells, controls c-myc expression by catalyzing the citrullination of histone H3 on its promoter. Results strongly suggest that PAD4 regulates the proliferation of multipotent progenitors in the bone marrow by controlling c-myc expression. [Nat Commun] Abstract

Generation of Engraftable Hematopoietic Stem Cells from Induced Pluripotent Stem Cells by Way of Teratoma Formation
Investigators demonstrated a unique in vivo differentiation system yielding engraftable hematopoietic stem cells from mouse and human induced pluripotent stem cells in teratoma-bearing animals in combination with a maneuver to facilitate hematopoiesis. [Mol Ther] Abstract

Pbx1 Restrains Myeloid Maturation while Preserving Lymphoid Potential in Hematopoietic Progenitors
Through analysis of purified progenitor proliferation, differentiation capacity and transcriptional profiling, researchers demonstrated that Pbx1 regulates the lineage-specific output of multipotent and oligopotent progenitors. In the absence of Pbx1 multipotent progenitor and common myeloid progenitor pools are reduced due to aberrantly rapid myeloid maturation. [J Cell Sci] Abstract

Caspase-3 Is Involved in the Signaling in Erythroid Differentiation by Targeting Late Progenitors
Using a culture system which renders nearly 100% enucleated red cells from human CD34+ cells, scientists investigated the role of active caspase-3 in erythropoiesis. [PLoS One] Full Article

CLINICAL RESEARCH

A No-Prophylaxis Platelet-Transfusion Strategy for Hematologic Cancers
The effectiveness of platelet transfusions to prevent bleeding in patients with hematologic cancers remains unclear. This trial assessed whether a policy of not giving prophylactic platelet transfusions was as effective and safe as a policy of providing prophylaxis. [N Engl J Med] Abstract | Press Release

Clinical Role of MicroRNAs in Cytogenetically Normal Acute Myeloid Leukemia: miR-155 Upregulation Independently Identifies High-Risk Patients
Investigators aimed to evaluate the impact of miR-155 on the outcome of adults with cytogenetically normal acute myeloid leukemia in the context of other clinical and molecular prognosticators and to gain insight into the leukemogenic role of this microRNA. [J Clin Oncol] Abstract | Press Release

A Distinct Evolution of the T Cell Repertoire Categorizes Treatment Refractory Gastrointestinal Acute Graft-versus-Host Disease
Investigators found that T cell receptor β CDR3 repertoire sequencing revealed patterns that could eventually serve as a disease biomarker of T cell alloreactivity in acute graft versus host disease (aGvHD). They identified T cell clones in gastrointestinal (GI) biopsies in a heterogeneous group of 15 allogeneic hematopoietic stem cell transplantation patients with GI aGvHD symptoms. [Blood] Abstract

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REVIEWS
Clinical Significance of Minimal Residual Disease in Patients with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation
Scientists review the clinical significance of minimal residual disease in the context of autologous and allogeneic hematopoietic stem cell transplantation. [Br J Haematol] Abstract

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

SMi's Cell Culture Conference July 3-4, 2013 in London, United Kingdom
INDUSTRY NEWS

Lilly Announces Enzastaurin Phase III Study Did Not Meet Primary Endpoint in Diffuse Large B-Cell Lymphoma
Eli Lilly and Company announced Phase III clinical trial results from enzastaurin’s PRELUDE study, which explored the molecule as a monotherapy in the prevention of relapse in patients with diffuse large B-cell lymphoma. The study failed to show a statistically significant increase compared to placebo in disease-free survival in patients at high risk of relapse following rituximab-based chemotherapy. [Eli Lilly and Company] Press Release

SymBio Initiates Japanese Phase II Trial for TREAKISYM® (Bendamustine) in CLL
SymBio Pharmaceuticals Limited announced that it commenced enrollment in a Phase II clinical trial in Japan for bendamustine hydrochloride (TREAKISYM®) in chronic lymphocytic leukemia (CLL) patients. [SymBio Pharmaceuticals Limited] Press Release

Onconova Completes Enrollment in ONTIME Pivotal Phase III Study of Rigosertib in Patients with High-Risk Myelodysplastic Syndromes
Onconova Therapeutics, Inc. announced it has reached its enrollment goal of 270 for its pivotal Phase III ONTIME trial of rigosertib in patients with myelodysplastic syndromes who have failed prior therapy with hypomethylating agents. [Onconova Therapeutics, Inc.] Press Release

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POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)
 
European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS
NEW Hydra IX Summer School on Stem Cell Biology
September 7-14, 2013
Hydra, Greece

Visit our events page to see a complete list of events in the hematopoietic community.
JOB OPPORTUNITIES
NEW Postdoctoral Fellow – Stem Cells and Cancer (Tsinghua University)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Position (Inselspital Bern, University Hospital Bern)

Postdoctoral Fellow – Myeloproliferative Neoplasms (Mount Sinai Medical Center)

Postdoctoral Positions – Stem Cell Biology and Aging (Children’s Hospital Oakland Research Institute)

Postdoctoral Positions (Cancer Science Institute of Singapore)

Postdoctoral Scholarship – Leukemia Stem Cell Biology (Lund University – Faculty of Medicine)

Studentship – Novel Mechanisms in Blood Cancers Drug-Resistance (University of East Anglia)


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