Hematopoiesis News Volume 11.04 | Feb 4 2020

TOP STORY

A Central Role of IKK2 and TPL2 in JNK Activation and Viral B-Cell Transformation

Investigators identified a novel and critical function of IκB kinase 2 (IKK2) and its co-factor NEMO in the activation of oncogenic c-Jun N-terminal kinase (JNK) signaling, induced by the latent membrane protein 1 (LMP1) of Epstein-Barr virus. Independent of its kinase activity, the TGFβ-activated kinase 1 mediates LMP1 signaling complex formation, NEMO ubiquitination and subsequent IKK2 activation. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Chromatin Mapping and Single-Cell Immune Profiling Define the Temporal Dynamics of Ibrutinib Response in CLL

Researchers identified a consistent regulatory program starting with a sharp decrease of NF-κB binding in chronic lymphocytic leukemia (CLL) cells, which was followed by reduced activity of lineage-defining transcription factors, erosion of CLL cell identity, and acquisition of a quiescence-like gene signature. [Nat Commun] Full Article

Loss of Kat2a Enhances Transcriptional Noise and Depletes Acute Myeloid Leukemia Stem-Like Cells

Through combined chromatin profiling and single-cell transcriptomics of a conditional knockout mouse, the authors demonstrated that Kat2a contributed to leukemia propagation through preservation of leukemia stem-like cells. Kat2a loss impacted transcription factor binding and reduces transcriptional burst frequency in a subset of gene promoters, generating enhanced variability of transcript levels. [eLife] Abstract

The mRNA-Binding Protein IGF2BP1 Restores Fetal Hemoglobin in Cultured Erythroid Cells from Patients with β-Hemoglobin Disorders

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is a fetal factor that undergoes a transcriptional switch consistent with the transition from fetal hemoglobin to adult hemoglobin. Lentivirus delivery of IGF2BP1 to CD34⁺ cells of healthy adult donors reversed hemoglobin production toward the fetal type in culture-differentiated erythroid cells. [Mol Ther Methods Clin Dev] Abstract | Full Article | Graphical Abstract

DNMT3A Mutants Provide Proliferating Advantage with Augmentation of Self-Renewal Activity in the Pathogenesis of AML in KMT2A-PTD-Positive Leukemic Cells

The authors found that overexpression of DNMT3A mutants in KMT2A-histone-lysine N-methyltransferase 2A-partial tandem duplication (PTD)-positive EOL-1 cells augmented cell proliferation and clonogenicity. Serial colony replating assays indicated that DNMT3A-mutants increased the self-renewal ability of Kmt2a-PTD-expressing mouse bone marrow cells with immature morphology. [Oncogenesis] Full Article

Spatial and Biochemical Interactions between Bone Marrow Adipose Tissue and Hematopoietic Stem and Progenitor Cells in Rhesus Macaques

Investigators employed optical clearing, confocal microscopy and nearest neighbor analysis to determine the spatial distribution of CD34⁺ hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) in a translationally relevant rhesus macaque model. Immunofluorescent analysis revealed that femoral BM adipocytes were associated with the branches of vascular sinusoids, with half of HSPCs localizing in close proximity of the nearest BM adipocyte. [Bone] Abstract

Cyclosporine H Improves the Multi-Vector Lentiviral Transduction of Murine Hematopoietic Progenitors and Stem Cells

The authors employed cyclosporine H for lentivirus transduction of murine hematopoietic stem cells and defined hematopoietic progenitors, confirming previous findings in more specific subsets of primitive hematopoietic cells. The data confirmed increased efficiencies, in agreement with the published data. [Sci Rep] Full Article

CLINICAL RESEARCH

Disease Risk and GvHD Biomarkers Can Stratify Patients for Risk of Relapse and Nonrelapse Mortality Post Hematopoietic Cell Transplant

Scientists tested whether the MAGIC algorithm probability could identify patients whose risk for relapse is higher than their risk for severe graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The multi-center study population was divided into two cohorts: historical and current with similar NRM, relapse, and survival. [Leukemia] Abstract

Occurrence of Long-Term Effects after Hematopoietic Stem Cell Transplantation in Children Affected by Acute Leukemia Receiving Either Busulfan or Total Body Irradiation: Results of an AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) Retrospective Study

The authors retrospectively analyzed in a population of 670 children receiving allogeneic hematopoietic stem cell transplantation for acute leukemia the occurrence of different late effects in function of the choice made between total body irradiation and busulfan, as part of the preparative regimen. [Bone Marrow Transplant] Abstract

Monitoring Minimal Residual/Relapsing Disease after Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia

Researchers retrospectively analyzed the contributions of lineage-sorted donor cell chimerism (sDCC) and quantitative PCR (qPCR) targeting disease-specific genetic rearrangements to detect minimal residual/relapsing disease and predict impending relapse in 94 adult adult lymphoblastic leukemia patients after stem cell transplantation. With a median follow-up of surviving patients of 3.3 years, qPCR and/or sDCC measurements turned positive in 38 patients. [Bone Marrow Transplant] Abstract

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Personal Tumor Antigens in Blood Malignancies: Genomics-Directed Identification and Targeting

The authors review the advances in systematic identification of minor histocompatibility antigens and neoantigens arising from personal somatic alterations or recurrent driver mutations. These exciting efforts pave the path for the implementation of personalized combinatorial cancer therapy. [J Clin Invest] Abstract

Immunotherapy for the Treatment of Acute Lymphoblastic Leukemia

The biologic and clinical contexts in which immunotherapies have advanced the treatment of acute lymphoblastic leukemia (ALL) confer optimism that more patients will achieve durable remissions. Immunotherapy treatments in ALL will expand through rationally targeted approaches alongside advances in CAR T cell therapy design and clinical experience. [Curr Oncol Rep] Abstract

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

Verastem Oncology Announces Dosing of First Patient in CSPC’s Chinese Study Evaluating COPIKTRA^® (Duvelisib) in Patients with Relapsed or Refractory Follicular Lymphoma

Verastem, Inc. announced that its partner CSPC Pharmaceutical Group Limited has dosed the first patient in a pivotal Chinese bridging study evaluating COPIKTRA^® in patients with relapsed or refractory follicular lymphoma. [Verastem Oncology, Inc.] Press Release

Moleculin Announces Successful Completion of US Phase I AML Trial of Annamycin

Moleculin Biotech, Inc. announced that its open label, single arm US Phase I trial met its primary objective of demonstrating the safety of Liposomal Annamycin in treating relapsed or refractory acute myeloid leukemia. [Moleculin Biotech, Inc.] Press Release

AbbVie Receives Positive CHMP Opinion for VENCLYXTO^® as a Chemotherapy-Free Combination Regimen for Patients with Previously Untreated Chronic Lymphocytic Leukemia

AbbVie announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has granted a positive opinion for VENCLYXTO^® in combination with obinutuzumab for the treatment of patients with chronic lymphocytic leukemia who were previously untreated. [AbbVie] Press Release

Children’s Hospital Los Angeles Receives $25 Million for Pediatric Cancer, Vision and Rehabilitation Programs

Children’s Hospital Los Angeles (CHLA) announced today that the Margie and Robert E. Petersen Foundation has contributed $25 million to establish an endowment supporting three of the hospital’s signature programs: the Cancer and Blood Disease Institute, the Vision Center and Inpatient Rehabilitation Services. [Children’s Hospital Los Angeles] Press Release

Why Did a Chinese University Hire Charles Lieber to Do Battery Research?

Among the ongoing mysteries surrounding last week’s arrest of Harvard University nanoscientist Charles Lieber is the precise nature of the research program Lieber was conducting in his cooperation with Chinese researchers. [ScienceInsider] Editorial

Cash from Cannabis Companies Creates Conflicted Researchers

Imagine that scientists charged with doing research on tobacco’s health implications were funded by tobacco companies. In fact, the tobacco industry used this tactic for decades to cast doubt on the adverse health effects of smoking. But today it would be an outrageous conflict of interest – research on addictive drugs shouldn’t be paid for by people who stand to profit from selling them. Yet this is exactly what is happening with cannabis. [STAT News] Editorial

NEW Tumor Metabolism
March 8-12, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Researcher – Bioinformatics and Leukemia Stem Cells (The Centre for Genomic Regulation)

Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Hereditary and Childhood Tumors (The University of British Columbia)

Postdoctoral Fellowship – Personalized Cancer Treatments (MGH Cancer Center)

Team Leader – Clonal Evolution in Leukemia (Institute of Cancer Research)

Faculty Position – Cancer Epidemiology (MD Anderson Cancer Center)

Research Fellow – Hematology & Blood Disorders (New York Blood Center)

Postdoctoral Fellow – Erythropoiesis (Mount Sinai School of Medicine)

Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine)

Associate/Professor – Hematology & Oncology (UC Davis School of Medicine)

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