Hematopoiesis News Volume 7.38 | Sep 27 2016

TOP STORY

Discovery of Dual Inhibitors of MDM2 and XIAP for Cancer Treatment

Researchers showed that the compound-induced MDM2 downregulation resulted not only in inhibition of XIAP expression, but also in activation of p53, which contributed to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo. One of the MDM2/XIAP inhibitors, MX69, showed minimal inhibitory effect on normal human hematopoiesis in vitro and was very well tolerated in animal models. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Mesenchymal Inflammation Drives Genotoxic Stress in Hematopoietic Stem Cells and Predicts Disease Evolution in Human Pre-Leukemia

Investigators showed that perturbation of mesenchymal cells in a mouse model of the pre-leukemic disorder Shwachman-Diamond syndrome induces mitochondrial dysfunction, oxidative stress, and activation of DNA damage responses in hematopoietic stem and progenitor cells. [Cell Stem Cell] Abstract | Graphical Abstract

The Ubiquitin Ligase Huwe1 Regulates the Maintenance and Lymphoid Commitment of Hematopoietic Stem Cells

Investigators identified the ubiquitin ligase Huwe1 as a crucial regulator of hematopoietic stem cell (HSC) function via its post-translational control of the oncoprotein N-myc. They found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid-fate specification in mice. [Nat Immunol] Abstract

MOZ (KAT6A) Is Essential for the Maintenance of Classically Defined Adult Hematopoietic Stem Cells

Scientists used the deletion of the monocytic leukemia zinc finger gene (Moz/Kat6a/Myst3) to examine the effects of removing hematopoietic stem cells (HSCs). Loss of MOZ, in adult mice leads to the rapid loss of HSCs as defined by transplantation. [Blood] Abstract

Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

The authors attempted to generate induced pluripotent (iPSC) stem cells from different subtypes of B-acute lymphoid leukemias to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. [Stem Cell Reports] Full Article | Graphical Abstract

miR-150 Exerts Antileukemia Activity In Vitro and In Vivo through Regulating Genes in Multiple Pathways

Researchers found that miR-150 is downregulated in samples from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, and normalized after patients achieved complete remission. [Cell Death Dis] Full Article

Rapid and Label-Free Microfluidic Neutrophil Purification and Phenotyping in Diabetes Mellitus

The authors present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus patients using small blood volumes. The developed inertial microfluidics technology enables single-step neutrophil isolation without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. [Sci Rep] Full Article | Press Release

Novel α-Substituted Tropolones Promote Potent and Selective Caspase-Dependent Leukemia Cell Apoptosis

Researchers evaluated the antiproliferative mechanisms of α-naphthyl tropolone and the related α-benzodioxinyl analog. The α-substituted tropolones inhibit growth of lymphocytic leukemia cells, but not healthy blood cells, with nanomolar potency. [Pharmacol Res] Abstract

CLINICAL RESEARCH

Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia

Investigators showed treatment with rituximab has improved the outcome for patients with non-Hodgkin’s lymphoma. Patients with B-lineage acute lymphoblastic leukemia may also have the CD20 antigen, which is targeted by rituximab. Scientists showed that adding rituximab to the acute lymphoblastic leukemia (ALL) chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. [N Engl J Med] Abstract

Cytokine-Induced Memory-Like Natural Killer Cells Exhibit Enhanced Responses against Myeloid Leukemia

Scientists demonstrated that human memory-like natural killer (NK) cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human acute myeloid leukemia (AML) blasts in vitro. In the context of a first-in-human Phase I clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. [Sci Transl Med] Abstract | Press Release

PR1 Peptide Vaccine Induces Specific Immunity with Clinical Responses in Myeloid Malignancies

PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes that preferentially kill leukemia and contribute to cytogenetic remission. Investigators conducted a Phase I/II trial to evaluate the safety, immunogenicity and clinical activity of the PR1 vaccination. [Leukemia] Abstract

ZNF384-Related Fusion Genes Consist of a Subgroup with a Characteristic Immunophenotype in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia

Scientists observed that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners. [Haematologica] Full Article

BCR-ABL (Ph)-Like Acute Leukemia-Pathogenesis, Diagnosis and Therapeutic Options

The authors review the biological mechanisms and diagnostic and clinical challenges presented by BCR-ABL (Ph)-like acute leukemias. [Blood Rev] Abstract

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

$10 Million Gift Creates Bursky Center for Human Immunology and Immunotherapy

Washington University School of Medicine in St. Louis has received a $10 million gift to support research that harnesses the immune system to fight cancer, infectious diseases, and disorders caused by autoimmunity and immune deficiencies. [Washington University School of Medicine] Press Release

Ibrutinib (IMBRUVICA^®) Supplemental New Drug Application Submitted to the U.S. Food and Drug Administration (FDA) for Marginal Zone Lymphoma (MZL)

Janssen Research & Development, LLC announced that a supplemental New Drug Application for ibrutinib (IMBRUVICA^®) has been submitted to the U.S. Food and Drug Administration for the treatment of patients with marginal zone lymphoma who require systemic therapy. The filing is based on data from the multi-center, open-label Phase II PCYC-1121 trial assessing the use of ibrutinib, a BTK inhibitor, in patients with MZL who have received at least one prior therapy. [Janssen Research & Development, LLC] Press Release

Kite Pharma Announces Positive Topline KTE-C19 Data from ZUMA-1 Pivotal Trial in Patients with Aggressive Non-Hodgkin Lymphoma (NHL)

Kite Pharma, Inc. announced positive topline results from a pre-planned interim analysis of ZUMA-1 for its lead product candidate, KTE-C19, in patients with chemorefractory diffuse large B-cell lymphoma. KTE-C19 met the primary endpoint of objective response rate (ORR) with 76 percent, including 47 percent complete remissions. [Kite Pharma, Inc.] Press Release

Syros Announces First Patient Enrolled in Phase II Clinical Trial of SY-1425 in Genomically Defined Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome

Syros Pharmaceuticals announced that the first patient has been dosed in the Phase II clinical trial of its lead drug candidate, SY-1425, a first-in-class selective retinoic acid receptor alpha agonist, in genomically defined subsets of patients with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndrome identified using a novel biomarker discovered by its gene control platform. [Syros Pharmaceuticals] Press Release

Science’s 1%: How Income Inequality Is Getting Worse in Research

Wages for top scientists are shooting skywards while others are being left behind. [Nature News] Editorial

Zimbabwean Scientists Fight to Preserve National Academy

Following years of chronic funding shortages and political neglect, the Zimbabwe Academy of Science (ZAS) is on its knees and has made a plea for support from the large Zimbabwean diaspora. The academy has historically survived on donations and membership fees, but this is no longer sustainable, said ZAS head Christopher Mutambirwa at a meeting of Zimbabwean expatriates in Johannesburg, South Africa. At the moment, the ZAS’s activities are voluntary and unpaid. [Nature News] Editorial

Four Men and Two Women Are Running for the Top Slot at the World Health Organization

The World Health Organization in Geneva, Switzerland, unveiled the names of the six candidates who are vying to succeed Margaret Chan as director-general. [Science Insider] Editorial

NEW 2016 World Cancer Congress
October 31-November 3, 2016
Paris, France

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

NEW Research Associate – Hematology (Editas Medicine)

NEW Faculty – Stem Cell Transplantation and Regenerative Medicine (Stanford University Medical School)

NEW Postdoctoral Position – Hematology and Gene Therapy (Cincinnati Children’s Research Foundation)

NEW Postdoctoral Position – Leukemia and Marrow Failure (H. Leighton Grimes) (Cincinnati Children’s Research Foundation)

Research Technologist – Hematopoietic Product Development (STEMCELL Technologies)

Postdoctoral Positions – Stem Cell Research, Hematopoiesis, Cancer, Genome Editing (Icahn School of Medicine)

Postdoctoral Fellowship – Gene Regulation and Leukemia (Cantor Laboratory Boston Children’s Hospital)

Assistant Associate/Member Faculty – Myeloid Malignancies (Fred Hutchinson Cancer Research Center)

Assistant, Associate or Full Professor – Normal and Malignant Hematopoiesis (Cincinnati Children’s Research Foundation)

Postdoctoral Position – Experimental Hematology and Cancer Biology (Cincinnati Children’s Research Foundation)

Research Fellow – Cancer Biology (University of Michigan)

PhD – Tumor Microenvironment in Leukemia (Georg-Speyer-Haus)

Postdoctoral Scholar – Tumor Biology (The Pennsylvania State University College of Medicine)

Research Technologist (Pennsylvania State University)

Postdoctoral Stipend – Development of Immune System (Lund University)

Principal Investigator & Clinical Geneticist – Pediatric Leukemia (Children´s Cancer Research Institute, St. Anna Kinderkrebsforschung)

Postdoctoral Research Scientist (National Taiwan University)

Assistant Member Faculty – Platinum/Immunotherapy (Fred Hutchinson Cancer Research Center)

Cytogenetics Laboratory Supervisor (Fred Hutchinson Cancer Research Center)

Assistant/Associate/Full Member Faculty – Myeloid Malignancies (Fred Hutchinson Cancer Research Center)

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