Hematopoiesis News Volume 9.10 | Mar 13 2018

TOP STORY

Researchers Identify Renegade Cells that Portend Relapse in Children with Leukemia

Researchers developed a technique that allowed them to determine at diagnosis whether children with acute lymphoblastic leukemia would relapse following treatment. [Press release from Stanford Medicine discussing online prepublication in Nature Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Exploiting an Asp-Glu “Switch” in Glycogen Synthase Kinase 3 to Design Paralog-Selective Inhibitors for Use in Acute Myeloid Leukemia

The glycogen synthase kinase 3-selective compound BRD0705 inhibited kinase function and did not stabilize β-catenin, mitigating potential neoplastic concerns. BRD0705 induced myeloid differentiation and impaired colony formation in acute myeloid leukemia cells, with no apparent effect on normal hematopoietic cells. [Sci Transl Med] Abstract

Setd2 Deficiency Impairs Hematopoietic Stem Cell Self-Renewal and Causes Malignant Transformation

Using a conditional Setd2 knockout mouse model, scientists showed that Setd2 deficiency skews hematopoietic differentiation and reduces the number of multipotent progenitors; although the number of phenotypic hematopoietic stem cells in Setd2-deleted mice is unchanged, functional assays, including serial BM transplantation, revealed that the self-renewal and competitiveness of HSCs are impaired. [Cell Res] Abstract

LKB1, Salt-Inducible Kinases, and MEF2C Are Linked Dependencies in Acute Myeloid Leukemia

Investigators used a domain-focused CRISPR screen to reveal an essential role for LKB1 and its salt-inducible kinase effectors to maintain MEF2C function in acute myeloid leukemia. [Mol Cell] Abstract | Press Release | Graphical Abstract

Targeting PFKFB3 Sensitizes Chronic Myelogenous Leukemia Cells to Tyrosine Kinase Inhibitor

Researchers showed that targeting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) sensitizes chronic myeloid leukemia (CML) cells to tyrosine kinase inhibitors and PFKFB3 may be a potential BCR-ABL kinase activity-independent mechanism in CML. [Oncogene] Abstract

Splenic Hematopoietic Stem Cells Display a Pre-Activated Phenotype

Scientists found that myeloid translocation gene 16 (Mtg16) deficiency in C57BL/6 mice resulted in significantly increased S-G2-M entry of splenic but not bone marrow HSC, suggesting that Mtg16 is an intrinsic negative regulator of G1-S transition in splenic HSC. [Immunol Cell Biol] Abstract

In Vivo Selection with Lentiviral Expression of Bcl2^{T69A/S70A/S87A} Mutant in Hematopoietic Stem Cell-Transplanted Mice

The authors developed a new in vivo selection system with the non-phosphorylatable Bcl2 mutant Bcl2^{T69A/S70A/S87A} (Bcl2^AAA), which makes in vivo selection drug independent and without risk of cytotoxicity or tumorigenesis. [Gene Ther] Abstract

High-Level Embryonic Globin Production with Efficient Erythroid Differentiation from a K562 Erythroleukemia Cell Line

Researchers developed an in vitro K562 erythroid differentiation model with high-level globin production. This model provided a practical evaluation tool for hemoglobin production in human erythroid cells. [Exp Hematol] Abstract

CLINICAL RESEARCH

Pacritinib vs Best Available Therapy, including Ruxolitinib, in Patients With Myelofibrosis

Investigators compared the efficacy and safety of JAK2 inhibitor pacritinib with that of best available therapy, including ruxolitinib, in patients with myelofibrosis and thrombocytopenia. [JAMA Oncol] Full Article | Press Release

Effect of Sorafenib on the Outcomes of Patients with FLT3-ITD Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Scientists evaluated the effect of sorafenib on the outcomes of patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3)–internal tandem duplication (ITD) undergoing allogeneic hematopoietic stem cell transplantation. [Cancer] Abstract

New Genetic Tools for the In Vivo Study of Hematopoietic Stem Cell Function

The authors discuss the development of novel HSC-specific genetic reporter systems that enable the prospective identification of HSCs and study of their functions in the absence of transplantation. [Exp Hematol] Abstract

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

Boehringer Ingelheim and Vanderbilt University Expand Partnership to Develop Novel Treatment Approaches for Cancer

Boehringer Ingelheim and Vanderbilt University collaborate to develop novel anti-cancer drugs that inhibit the myeloid cell leukemia 1 protein. [Boehringer Ingelheim Pharmaceutical] Press Release

Bioverativ Announces First Patient Dosed in Phase III Study of BIVV009 for Treatment of Cold Agglutinin Disease

Bioverativ Inc. announced that the first patient has been dosed in the Phase III clinical program of its investigational therapy BIVV009 for cold agglutinin disease. [Bioverativ Inc.] Press Release

UC San Diego Researchers Launch Combination Drug Trial to Eradicate B-Cell Malignancies

Fueled by a multimillion dollar grant from the state’s stem cell agency, researchers at University of California San Diego School of Medicine, in collaboration with Oncternal Therapeutics, have launched a Phase Ib/II clinical trial to evaluate the combined effectiveness of a standard of care drug with a novel monoclonal antibody that target B-cell malignancies, which include leukemias and lymphomas. [University of California, San Diego] Press Release

Seattle Genetics Initiates New Phase I Study in Relapsed or Refractory Multiple Myeloma

Seattle Genetics, Inc. announced dosing of the first patient in a Phase I clinical trial evaluating the safety and tolerability of SGN-CD48A for patients with relapsed or refractory multiple myeloma (MM). SGN-CD48A is an investigational antibody-drug conjugate targeted to the protein CD48, which is highly expressed on MM cells. [Seattle Genetics, Inc.] Press Release

Actinium Announces FDA Clearance of IND for Phase I Trial of Actimab-A in Combination with CLAG-M for Patients with Relapsed or Refractory AML

Actinium Pharmaceuticals, Inc. announced that the Medical College of Wisconsin received clearance from the FDA for the previously announced Investigational New Drug application for the Phase I trial of Actimab-A in combination with CLAG-M for relapsed or refractory acute myeloid leukemia (AML) patients. [Actinium Pharmaceuticals, Inc.] Press Release

Bellicum Announces Interim Results Showing Low Rates of Cancer Recurrence in Pediatric AML Patients Treated with BPX-501

Bellicum Pharmaceuticals, Inc. reported interim clinical data of BPX-501 in pediatric patients with acute myeloid leukemia (AML) and primary immunodeficiencies. [Bellicum Pharmaceuticals, Inc.] Press Release

Russian Science Chases Escape from Mediocrity

After letting Russian science languish for years, Vladimir Putin has started to pay more attention. At a meeting of the Council for Science and Education, the Russian president promised that science and innovation are now top priorities. [Nature News] Editorial

University Strikes to Continue after Staff Reject Pension Offer

Strikes at UK universities are to continue after staff overwhelmingly rejected a revised offer on their pensions. [The Guardian] Editorial

Key Republican Lawmaker Releases New ‘Right-to-Try’ Legislation

A key Republican lawmaker released a new version of so-called “right to try” legislation, a pivotal next step in the effort to help dying patients get access to experimental therapies. [STAT News] Editorial

Scientists Win and Lose in Texas Primary Contests

Texas primary was the first test for scientists seeking seats in the U.S. House of Representatives, and the results were mixed. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Extracellular Vesicles
August 19-24, 2018
Newry, Maine, United States

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

NEW Postdoctoral Fellow – Hematopoietic Stem Cells, Leukemia and Cancer Biology (Washington University School of Medicine, St. Louis)

NEW Postdoctoral Position – Tregs in the Hematopoietic Stem Cell Niche (Columbia University)

Postdoctoral Associate – Stem Cell Biology and Cancer Epigenetics (The Jackson Laboratory)

Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine)

Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Positions – Hematopoietic Stem Cells (Memorial Sloan Kettering Cancer Center)

Postdoctoral Scientist – Haematopoietic Stem Cell Biology (University of Oxford)

Postdoctoral Associate – Stem Cell Biology (Duke University)

Postdoctoral Fellowship – Functional Genomics of Human Hematopoiesis (Harvard Medical School)

Postdoctoral Scholar – Leukemia (University of Southern California)

Postdoctoral Research Fellow – Hematopoietic Stem Cell Development (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Positions – Translational Leukemia (NYU Langone School of Medicine)

Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia)

Postdoctoral Fellow Positions – Epigenetics, Hematopoietic Stem Cell Biology, Bioengineering, and Blood Cancers (Nationwide Childrens Hospital and Ohio State University)

PhD Student – Hematology, Oncology and Stem Cell Transplantation (University Medical Center Freiburg)

Postdoctoral position – Myeloma (MD Anderson Cancer Center)

Postdoctoral Position – Hematology and Cancer Biology (University of Florida)

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