Hematopoiesis News Volume 8.22 | Jun 6 2017

TOP STORY

Precision Therapy Enasidenib Effective in Treating Deadly Form of Leukemia

Some patients with relapsed or treatment-resistant acute myeloid leukemia, a form of blood cancer for which there are few treatments, may achieve remission with an experimental targeted therapy, according to early trial data. [Press release from the American Society of Hematology discussing online prepublication in Blood] Press Release | Abstract

(Ranked by impact factor of the journal)

Targeting Chronic Myeloid Leukemia Stem Cells with the Hypoxia-Inducible Factor Inhibitor Acriflavine

The authors addressed the effects of the pharmacological inhibition of hypoxia-inducible factor-1 (HIF-1), a critical regulator of leukemia stem cell survival, on the maintenance of chronic myeloid leukemia (CML) stem cell potential. They found that the HIF-1 inhibitor acriflavine decreased survival and growth of CML cells. [Blood] Abstract

Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells

Scientists utilized a clinically-relevant, immunomagnetic bead (IB)-based method to purify CD34⁺CD38^– cells from human bone marrow and mobilized peripheral blood. IB-purification of CD34⁺CD38^– cells enriched SCID repopulating cell frequency an additional 12-fold beyond standard CD34⁺ purification and did not affect gene marking of long-term hematopoietic stem cells. [Mol Ther] Abstract | Graphical Abstract

Reduced Hematopoietic Stem Cells Frequency Predicts Outcome in Acute Myeloid Leukemia

Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of a cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. [Haematologica] Abstract

Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a

Investigators showed that during serial bone marrow transplantation, hematopoietically-expressed homeobox transcription factor (Hhex)-deleted hematopoietic stem cells (HSCs) are progressively lost, revealing an intrinsic defect in HSC self-renewal. [Stem Cells] Abstract

Knockdown of miR-128a Induces Lin28a Expression and Reverts Myeloid Differentiation Blockage in Acute Myeloid Leukemia

Scientists found Lin28A underexpressed in blast cells from acute myeloid leukemia (AML) patients and AML cell lines as compared with CD34⁺ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes. [Cell Death Dis] Full Article

Inflammatory Mediator Ultra-Low-Molecular-Weight Hyaluronan Triggers Necrosis of B-Precursor Leukemia Cells with High Surface CD44 Expression

Researchers investigated biological effects of hyaluronan (HA) with different molecular sizes on mixed lineage leukemia gene rearrangements (MLL+ALL) cell lines, and found that the addition of ultra-low-molecular-weight-HA strongly suppressed their thymidine uptakes. The MLL+ALL cell line lacking surface CD44 expression established by genome editing showed no suppression of thymidine uptake. [Cell Death Dis] Full Article

Bone Marrow Niche-Mimetics Modulate HSPC Function via Integrin Signaling

The authors used bone marrow-mimetic decellularized extracellular matrix (ECM) scaffolds derived from mesenchymal stromal cells to study hematopoietic stem and progenitor cell (HSPC)-ECM interaction. [Sci Rep] Full Article

Directionality of Non-Permissive HLA-DPB1 T-Cell Epitope Group Mismatches Does Not Improve Clinical Risk Stratification in 8/8 Matched Unrelated Donor Hematopoietic Cell Transplantation

Investigators showed significantly higher in vitro relative responses to bi-directional mismatches compared with uni-directional host vs graft or graft vs host mismatches in a total of 420 one-way mixed lymphocyte reactions between 10/10 matched pairs. [Bone Marrow Transplant] Abstract

CLINICAL RESEARCH

A Phase I/II Minor Histocompatibility Antigen-Loaded Dendritic Cell Vaccination Trial to Safely Improve the Efficacy of Donor Lymphocyte Infusions in Myeloma

Scientists treated nine multiple myeloma patients with persistent or relapsed disease after allogeneic stem cell transplantation and a previous donor lymphocyte infusion (DLI), with donor monocyte-derived mHag-peptide-loaded dendritic cell vaccinations combined with a second DLI. Vaccinations were well tolerated and no occurrence of GvHD was observed. [Bone Marrow Transplant] Abstract

Reduced Toxicity, Myeloablative HLA-Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Sickle Cell Disease

The authors hypothesized that combining post-transplantation cyclophosphamide with a myeloablative reduced toxicity conditioning including serotherapy to increase immune ablation would allow for better engraftment. In a pilot approach, they treated three patients with sickle cell disease lacking a matched donor. All patients had severe disease-related complications despite standard treatment. They received unmanipulated bone marrow from parental HLA-haploidentical donors. [Ann Hematol] Abstract

Heparan Sulfate Proteoglycans as Key Regulators of the Mesenchymal Niche of Hematopoietic Stem Cells

The key regulatory effects of major medullar heparan sulfate proteoglycans are described, focusing on their roles in the interactions between hematopoietic stem cells and their endosteal niche, and on their ability to interact with heparin binding proteins. [Glycoconj J] Abstract

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

Helsinn Group and MEI Pharma Report Correlation between Mutations in DNA Methylation Pathway and Clinical Response in Phase II Study of Pracinostat and Azacitidine in Acute Myeloid Leukemia

Helsinn and MEI Pharma, Inc. announced findings from a genetic mutation analysis of patients in a Phase II clinical study of the investigational drug pracinostat and azacitidine in acute myeloid leukemia, including a significant correlation between genetic mutations in the DNA methylation pathway and clinical response. [Press release from MEI Pharma, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, Chicago] Press Release

City of Hope Presents New Studies

City of Hope physicians and researchers will present their latest research on blood stem cell transplants for HIV patients, immunotherapies, unique treatment options for older adults battling breast cancer and other topics. [Press release from City of Hope discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, Chicago] Press Release

Exploratory Analysis of the Phase I/II CHRYSALIS Study of Gilteritinib Demonstrates First Molecular Response to FLT3 Inhibitor in Acute Myeloid Leukemia

Astellas announced data from an exploratory analysis of the Phase I/II CHRYSALIS study, which demonstrated that FLT3 mutation-positive relapsed/refractory acute myeloid leukemia patients with molecular response had improved overall survival compared with those without a molecular response when treated with either 120 mg/day or 200 mg/day doses of gilteritinib, a FLT3/AXL inhibitor. [Press release from Astellas Pharma US, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, Chicago] Press Release

Bristol-Myers Squibb and Seattle Genetics Expand Clinical Collaboration to Evaluate Combination of Opdivo (Nivolumab) and ADCETRIS^® (Brentuximab Vedotin) in Pivotal Phase III Clinical Trial in Relapsed Hodgkin Lymphoma

Bristol-Myers Squibb Company and Seattle Genetics, Inc. announced that the companies have entered into a collaboration agreement to evaluate the combination of Bristol-Myers Squibb’s immunotherapy Opdivo and Seattle Genetics’ antibody-drug conjugate ADCETRIS in a pivotal Phase III clinical trial. [Bristol-Myers Squibb Company] Press Release

Jazz Pharmaceuticals Announces FDA Acceptance of NDA for VYXEOS™ (CPX-351), an Investigational Treatment for Acute Myeloid Leukemia, with Priority Review Status

Jazz Pharmaceuticals plc announced that the U.S. Food and Drug Administration (FDA) has accepted for filing with Priority Review its recently submitted New Drug Application (NDA) for VYXEOS™ liposome injection, an investigational treatment for acute myeloid leukemia. [Jazz Pharmaceuticals] Press Release

Romania’s Science Reforms Prompt Boycott

Researchers in Romania are stepping up protests against controversial government science reforms. Hundreds of scientists at leading research institutions say they will refuse to sit on national panels that assess and award grants, after the Romanian researchers’ association Ad Astra called for the boycott. But not all scientists in the country support the move. [Nature News] Editorial

NIH Plan to Reduce Overhead Payments Draws Fire

President Donald Trump’s administration has brought a long-simmering debate over how the U.S. government supports university research back to a boil. In its 2018 budget proposal, the White House proposes cutting so-called indirect cost payments that the National Institutes of Health (NIH) makes to universities, hospitals, and research institutes by about two-thirds, to 10% of each grant. The administration says the change would allow it to redirect about $4.6 billion now spent each year on overhead—including maintaining labs and complying with regulations—to research. [ScienceInsider] Editorial

NEW ASCO/AACR Methods in Clinical Cancer Research Workshop
July 29-August 4, 2017
Vail, United States

NEW Standardization of the Hematopoietic Progenitor Assay Training Course
October 11-12, 2017
Vancouver, Canada

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

NEW Postdoctoral Position – Genetic Engineering of Lymphocytes for Treatment of Leukemia (Karolinska Institutet)

Postdoctoral Fellow – Stem Cell Biology and Epigenetics (University of South Carolina)

Postdoctoral Fellow – Single Cell Sequencing (University of British Columbia Mechanical Engineering)

Postdoctoral Fellow – Hematopoietic Chimeras (Children’s Hospital of Chicago and Northwestern University)

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

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

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

Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

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)

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