Hematopoiesis News Volume 8.37 | Sep 19 2017

TOP STORY

Epigenetic Code Plays a Role in Acute Myeloid Leukemia

Dr. Samie Jaffrey, professor of pharmacology at Weill Cornell Medicine, and Michael Kharas, assistant member in pharmacology at Memorial Sloan Kettering Cancer Center, showed that people with acute myeloid leukemia (AML) have unusually high levels of an enzyme that places chemical marks on mRNA. Reducing levels of the enzyme, the investigators found, caused tumor cells from patients with AML to begin behaving more like normal cells. [Press release from Cornell University discussing online prepublication in Nature Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Lifelong Hematopoiesis Is Established by Hundreds of Precursors throughout Mammalian Ontogeny

The authors used the sample-to-sample variance of a multicolored lineage trace reporter to assess the frequency of emerging lifelong blood progenitors while avoiding the disruption, culture or transplantation of embryos. They found that approximately 719 Flk1⁺ mesodermal precursors, 633 VE-cadherin⁺ endothelial precursors and 545 Vav1⁺ nascent blood stem and progenitor cells emerge to establish the hematopoietic system at embryonic days (E)7–E8.5, E8.5–E11.5 and E11.5–E14.5, respectively. [Nat Cell Biol] Abstract | Press Release

Therapeutic Gene Editing in CD34⁺ Hematopoietic Progenitors from Fanconi Anemia Patients

Scientists conducted therapeutic gene editing in clinically relevant cells, such as HSCs. Using primary cord blood CD34⁺ cells from healthy donors, gene targeting was confirmed not only in in vitro cultured cells, but also in hematopoietic precursors responsible for the repopulation of primary and secondary immunodeficient mice. [EMBO Mol Med] Full Article | Graphical Abstract

Senescence Is a Spi1/PU.1-Induced Anti-Proliferative Mechanism in Primary Hematopoietic Cells

Investigators explored whether cellular senescence, an anti-tumoral pathway that restrains cell proliferation, is a mechanism by which Spi1 limits hematopoietic cells expansion, and thus prevents the development of leukemia. They showed that Spi1 overexpression triggers cellular senescence both in primary fibroblasts and hematopoietic cells. [Haematologica] Full Article

Defective Erythropoiesis Caused by Mutations of the Thyroid Hormone Receptor α Gene

Using Thra1^PV/+ mice, the authors explored how the TRα1PV mutant acted to cause abnormalities in erythropoiesis. Thra1^PV/+ mice exhibited abnormal red blood cell indices similarly as reported for patients. In vitro terminal differentiation assays showed a significant reduction of mature erythrocytes in Thra1^PV/+ mice. [PLoS Genet] Full Article

Whole Body and Hematopoietic ADAM8 Deficiency Does Not Influence Advanced Atherosclerotic Lesion Development, despite Its Association with Human Plaque Progression

Investigators examined the expression of A disintegrin and metalloproteinase 8 (ADAM8) in early and progressed human atherosclerotic lesions, in which ADAM8 was significantly upregulated in vulnerable lesions. ADAM8 expression was most prominent in the shoulder region of human atherosclerotic lesions, characterized by the abundance of foam cells. [Sci Rep] Full Article

Signaling of the Complement Cleavage Product Anaphylatoxin C5a through C5aR (CD88) Contributes to Pharmacological Hematopoietic Stem Cell Mobilization

Researchers demonstrated that mice deficient in the mannan-binding lectin pathway, which activates the proximal part of the complement cascade, as well as mice deficient in the fifth component of the complement cascade, which is part of the distal part of the complement cascade, are poor mobilizers. [Stem Cell Rev] Full Article

Enhancement of Mouse Hematopoietic Stem/Progenitor Cell Function via Transient Gene Delivery Using Integration-Deficient Lentiviral Vectors

The authors demonstrated the utility of short-term gene expression to improve functional potency of hematopoietic stem/progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using integration-deficient lentiviruses (IdLVs) to enhance the engraftment of HSPCs. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduced this risk and those associated with unsolicited gene expression in daughter cells. [Exp Hematol] Abstract

CLINICAL RESEARCH

Autologous Hematopoietic Cell Transplantation for Multiple Myeloma Patients with Renal Insufficiency: A Center for International Blood and Marrow Transplant Research Analysis

Autologous hematopoietic cell transplantation (AHCT) in multiple myeloma patients with renal insufficiency (RI) is controversial. Thirty four of thirty five patients with severe RI achieved post-AHCT dialysis independence. The five-year PFS for normal, moderate and severe RI was 35%, 40% and 27%, respectively. [Bone Marrow Transplant] Abstract

Early Blood Stream Infection following Allogeneic Hematopoietic Stem Cell Transplantation Is a Risk Factor for Acute Grade III–IV GVHD in Children and Adolescents

Scientists conducted a retrospective analysis to test the hypothesis that early blood stream infection (BSI) predisposes allogeneic pediatric transplant patients to severe acute graft-versus-host disease (GVHD). These results indicated that early BSI appears to be a risk factor for acute grade III–IV GVHD. [Pediatr Blood Cancer] Abstract

Mutations in Myeloproliferative Neoplasms – Their Significance and Clinical Use

The authors provide an overview of the mutational landscape of myeloproliferative neoplasms (MPNs), the impact of these mutations in MPN pathogenesis as well as their prognostic value. Finally, a summary of how these mutations are being used or could potentially be used for the treatment of MPN patients is presented. [Expert Rev Hematol] Abstract

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

Imara Reports Favorable Preclinical and Phase I Data on IMR-687 in Sickle Cell Disease

Imara Inc. reported additional preclinical and Phase I clinical data from the company’s lead compound, IMR-687, a once-daily, oral therapy designed to address the underlying pathology of sickle cell disease. [Press release from Imara Inc. discussing research presented at the 6^th Annual Sickle Cell Therapeutics Conference, New York] Press Release

MD Anderson and Daiichi Sankyo Enter Research Collaboration to Accelerate Development of Acute Myeloid Leukemia Therapies

The University of Texas MD Anderson Cancer Center and Daiichi Sankyo Company, Limited announced a multi-year collaboration focused on accelerating the development of novel therapies for acute myeloid leukemia. [Daiichi Sankyo Company, Limited] Press Release

CHLA Awarded $1.3 Million by NIH for Pediatric Blood and Marrow Transplantation Consortium

Michael Pulsipher, MD, of the Children’s Center for Cancer and Blood Diseases at the Children’s Hospital Los Angeles (CHLA) has been awarded $1.3 million by the National Heart, Lung, and Blood Institute of the NIH. The funding represents a Clinical Trial Network Core Center Renewal for the Pediatric Blood and Marrow Transplantation Consortium headquartered at CHLA. [Children’s Hospital Los Angeles] Press Release

Fate Therapeutics Initiates Phase II PROTECT Study of ProTmune^™ for Prevention of Acute Graft-versus-Host Disease

Fate Therapeutics, Inc. announced that the company initiated enrollment in the Phase II stage of PROTECT, a combined open-label Phase I/blinded Phase II clinical trial of ProTmune^™ for the prevention of acute graft-versus-host disease in patients with hematologic malignancies undergoing matched unrelated donor hematopoietic cell transplantation. [Fate Therapeutics, Inc.] Press Release

Imago BioSciences Doses First Patients in Phase I/II Study of IMG-7289 in Myelofibrosis

Imago BioSciences announced that the first patients have been dosed in a Phase I/II clinical trial of IMG-7289 for the treatment of myelofibrosis. IMG-7289 is an investigational therapeutic agent that suppresses the production of inflammatory cytokines that characterize myelofibrosis; IMG-7289 also impairs self-renewal and proliferation of neoplastic stem cells. [Imago BioSciences (PR Newswire Association LLC.)] Press Release

Sancilio Pharmaceuticals Company, Inc. (SPCI) Receives Rare Pediatric Disease Designation from the U.S. Food and Drug Administration for AltemiaTM a Treatment of Sickle Cell Disease (SCD) in Children

SPCI announced that the FDA has granted Rare Pediatric Disease designation to AltemiaTM Soft Gelatin Capsules for the treatment of SCD in children. AltemiaTM, a leading development program for SCPI, is being developed as an oral, once-a-day formulation for children between the ages of 5-17 with SCD. [Sancilio Pharmaceuticals Company, Inc.] Press Release

U.S. House Approves 2018 Spending Bills, but Process Far from Finished

The U.S. House of Representatives took a major step toward setting federal science budgets for the 2018 fiscal year. But Congress is still far from the finish line, and final spending levels aren’t likely to be finalized until late this year at the earliest. [ScienceInsider] Editorial

After Uproar, U.K. Parliament’s Science Committee Now Has a Female Member

The House of Commons Science and Technology Committee tweeted that it was “pleased to announced our membership has been confirmed.” Parliamentary committees had been dissolved after the recent U.K. election, and now the panel was rolling out its new contingent of lawmakers. The only problem: All eight of the mostly smiling faces belonged to men. [ScienceInsider] Editorial

They Got Hundreds of Thousands to Rally. Where Does the March for Science Go from Here?

The hundreds of thousands of people who rallied on the National Mall and in cities worldwide for the March for Science came to be noticed. But as two dozen of them met in New York the following month for a debrief, they faced an obvious reality: A grass-roots organization that was quickly formed to plan a singular event was not, at least immediately, equipped for far-reaching and long-term science advocacy. [STAT News] Editorial

NEW 2018 Blood and Marrow Transplantation (BMT) Tandem Meetings
February 21-25, 2018
Salt Lake City, Utah, United States

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

NEW Postdoctoral Fellowship – Functional Genomics of Human Hematopoiesis (Boston Children’s Hospital, Harvard Medical School)

NEW Postdoctoral Researcher – Cellular and Molecular Immunoregulation (International Clinical Research Center of St. Anne’s University Hospital Brno)

Postdoctoral Opportunities – Biology of Colorectal Cancer (Albert Einstein College of Medicine)

Postdoctoral Fellow – Cancer Biology (UCSF Benioff Children’s Hospital)

Postdoctoral Position – Hematopoietic Stem Cells and Malignancies (Albert Einstein College of Medicine)

Scientist – Regulators of Hematopoiesis (Università di Roma)

Postdoctoral Scholar – Hematopoiesis and Leukemia (Penn State College of Medicine)

Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre)

Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University)

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

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