Hematopoiesis News Volume 8.27 | Jul 11 2017

TOP STORY

Tracing the Origins of Relapse in Acute Myeloid Leukemia to Stem Cells

Through combined genetic and functional analysis of purified subpopulations and xenografts from paired diagnosis/relapse samples, scientists identified therapy-resistant cells already present at diagnosis and two major patterns of relapse. In some cases, relapse originated from rare leukemia stem cells with a hematopoietic stem/progenitor cell phenotype, while in other instances relapse developed from larger subclones of immunophenotypically committed leukemia cells that retained strong stemness transcriptional signatures. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

PDK1 Plays a Vital Role on Hematopoietic Stem Cell Function

Scientists specifically deleted the PDK1 gene in the hematopoietic system and found that PDK1-deficient HSCs exhibited impaired function and defective lineage commitment abilities. Lack of PDK1 caused HSCs to be less quiescent and to produce a higher number of phenotypic HSCs and fewer progenitors. [Sci Rep] Full Article

Inter-Strain Differences in LINE-1 DNA Methylation in the Mouse Hematopoietic System in Response to Exposure to Ionizing Radiation

Researchers investigated the endogenous DNA methylation status of the 5′ untranslated region of long interspersed nuclear element 1 (LINE-1) retrotransposons that are the major repetitive elements in mammalian genomes. They demonstrated that basal levels of DNA methylation within the 5′-UTRs of LINE-1 elements did not differ significantly between the two mouse strains and were negatively correlated with the evolutionary age of LINE-1 elements. [Int J Mol Sci] Full Article

Downregulation of the IFNAR1 Chain of Type 1 Interferon Receptor Contributes to the Maintenance of the Hematopoietic Stem Cells

The authors determined the role of IFNAR1 downregulation in the maintenance of HSCs. Mice harboring the ubiquitination-deficient Ifnar1^S526A allele displayed greater levels of hematopoietic cell progenitors but reduced numbers of the long-term HSCs compared to wild type mice and animals lacking Ifnar1. [Cancer Biol Ther] Abstract

Three-Dimensional Nano-Fiber Scaffold for Ex Vivo Expansion of Cord Blood Hematopoietic Stem Cells

Researchers studied the ex vivo expansion of cord blood (CB) HSCs in a new three-dimensional polycaprolactone nano-scaffold coated with fibronectin (FN). They isolated CB CD34⁺ cells and cultured for ten days in presence of growth factors. 3D PCL nano-scaffold coated with FN produced significantly higher total nucleated cells and CD34⁺ cells and also had significantly higher homing and self-renewal genes than 2D cell culture and before expansion. [Artif Cells Nanomed Biotechnol] Abstract

CLINICAL RESEARCH

Hematopoietic Stem Cell Transplantation in 29 Patients Hemizygous for Hypomorphic IKBKG / NEMO Mutations

Scientists report the health status before hematopoietic stem cell transplantation, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Transplantation did not appear to cure colitis, possibly due to cell-intrinsic disorders of the epithelial barrier. [Blood] Abstract

Safety and Tolerability of Deferasirox in Pediatric Hematopoietic Stem Cell Transplant Recipients: One Facility’s Five Years’ Experience of Chelation Treatment

42 pediatric patients with iron overload, who underwent liver biopsy and deferasirox treatment after hematopoietic stem cell transplantation were included in the study group. The authors recommended a close monitoring in pediatric hematopoietic transplant recipients subjected to deferasirox-based therapy because they observed a high incidence of adverse events and discontinuation of chelation treatment. [Oncotarget] Full Article

Stimulation of Adrenergic Activity by Desipramine Enhances Hematopoietic Stem and Progenitor Cell Mobilization along with G-CSF in Multiple Myeloma – A Pilot Study

Researchers present the results of an open-label single-arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation to assess the safety and efficacy of desipramine combined with G-SCF to induce HSC mobilization. [Am J Hematol] Abstract

Partial T-Cell Depletion Improves the Composite Endpoint Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation

Investigators compared graft-versus-host disease-free, relapse-free survival (GRFS) in patients receiving partial T-cell-depleted (pTCD) grafts with patients receiving T-cell-replete grafts. pTCD was associated with a significantly improved GRFS. They observed no effect of pTCD on overall survival, progression-free survival, and relapse cumulative incidence, while non-relapse mortality cumulative incidence was significantly lower in patients receiving pTCD. [Leuk Lymphoma] Abstract

The Road Map for Megakaryopoietic Lineage from Hematopoietic Stem/Progenitor Cells

The authors summarize recent findings about megakaryocytes differentiation from hematopoietic stem cells and discuss future directions in this research field. [Stem Cells Transl Med] Full Article

Identity of Gli1⁺ Cells in the Bone Marrow

A recent study by using state-of-the-art techniques including in vivo lineage-tracing provides evidence that Gli1+ cells are the cells responsible for fibrotic disease in the bone marrow. Strikingly, genetic depletion of Gli1⁺ cells rescues bone marrow failure and abolishes myelofibrosis. This work brings a new central cellular target for bone marrow fibrosis. The emerging knowledge from this research will be important for the treatment of several malignant and non-malignant disorders. [Exp Hematol] Abstract

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

FDA Advisory Committee Votes in Favor of Pfizer’s Mylotarg (Gemtuzumab Ozogamicin) for Acute Myeloid Leukemia

Pfizer Inc. announced that the U.S. FDA Oncologic Drug Advisory Committee voted that the results of ALFA-0701 demonstrated a favorable risk:benefit profile for MYLOTARG when added to chemotherapy for patients with newly-diagnosed CD33-positive acute myeloid leukemia. [Pfizer Inc.] Press Release

U.S. Food and Drug Administration Accepts for Priority Review Bristol-Myers Squibb’s Application for Sprycel (Dasatinib) in Children with Philadelphia Chromosome-Positive Chronic Phase Chronic Myeloid Leukemia

Bristol-Myers Squibb Company announced that the U.S. FDA accepted its supplemental New Drug Application to include an indication for Sprycel to treat children with Philadelphia chromosome-positive chronic phase chronic myeloid leukemia, as well as a powder for oral suspension formulation of Sprycel. [Bristol-Myers Squibb Company] Press Release

ViraCyte Completes Phase I Clinical Trial of Viralym-C

ViraCyte, LLC announced the successful completion of a Phase I clinical trial using Viralym-C, a “ready to administer” T cell immunotherapy product for the treatment of cytomegalovirus infection in hematopoietic stem cell transplant recipients. [ViraCyte, LLC.] Press Release

White House’s Dwindling Science Office Leaves Major Research Programs in Limbo

US President Donald Trump has pledged to shrink the federal government, and he seems to be starting with science. Nearly six months after taking office, Trump has not chosen a science adviser, and the White House’s Office of Science and Technology Policy has dwindled from around 130 staff members under former president Barack Obama to 35. [Nature News] Editorial

Trump Administration Chooses Georgia Physician to Lead US Public-Health Agency

Obstetrician and gynecologist Brenda Fitzgerald will direct the US Centers for Disease Control and Prevention, Secretary of Health and Human Services Tom Price announced. [Nature News] Editorial

French Scientist Fined for Failure to Disclose Industry Ties

In an unprecedented court case in Paris, an eminent French lung specialist has been fined €50,000 and given a six-month suspended jail sentence because he didn’t disclose his ties to the oil industry during a Senate air-pollution inquiry. [Nature News] Editorial

NEW Keystone Symposia: Lymphocytes and Their Roles in Cancer
February 11-15, 2018
Keystone, Colorado, United States

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NEW Postdoctoral Fellow – Regenerative Medicine (Loma Linda University)

Postdoctoral Fellow – Epigenetics of Hematopoiesis (International Clinical Research Center)

Senior/Principal Scientist – Stem Cell Research (Plasticell Ltd)

Postdoctoral Associate – Normal and Malignant Hematopoiesis (University of Miami)

PhD Studentship – Genome Editing of Hematopoietic Stem Cells (CHU Saint Justine Research Center)

Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals)

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)

Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel)

Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

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

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