Hematopoiesis News Volume 10.47 | Dec 3 2019

TOP STORY

HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-Like Disease in Mice

Investigators found that HOTTIP was aberrantly activated in acute myeloid leukemia (AML) to alter HOXA-driven topologically associated domain (TAD) and gene expression. HOTTIP loss attenuated leukemogenesis of transplanted mice, while reactivation of HOTTIP restored leukemic TADs, transcription, and leukemogenesis in the CTCF-boundary-attenuated AML cells. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

HMCES Functions in the Alternative End-Joining Pathway of the DNA DSB Repair during Class Switch Recombination in B Cells

The authors showed that Hmces-deficient mice displayed normal hematopoiesis without global alterations in 5-hydroxymethylcytosine. HMCES specifically enabled DNA double-strand break repair through the microhomology-mediated alternative-end-joining pathway during class switch recombination (CSR) in B cells, and HMCES deficiency led to a significant defect in CSR. [Mol Cell] Abstract | Graphical Abstract

Immunosuppression by Mutated Calreticulin Released From Malignant Cells

Researchers used the retention using selective hooks assay to monitor the trafficking of C-terminally modified calreticulin (CALR). They found that exon-9-mutated CALR was released from cells in response to the biotin-mediated detachment from its ER-localized hook, in vitro and in vivo. Cellular CALR release was confirmed in suitable mouse models bearing exon-9-mutated hematopoietic systems or tumors. [Mol Cell] Abstract | Graphical Abstract

Myeloid Lineage Enhancers Drive Oncogene Synergy in CEBPA/CSF3R Mutant Acute Myeloid Leukemia

Scientists demonstrated that activating mutations in the granulocyte colony stimulating factor receptor (CSF3R) cooperated with loss of function mutations in the transcription factor CEBPA to promote acute leukemia development. The interaction between these distinct classes of mutations occured at the level of myeloid lineage enhancers where mutant CEBPA prevented activation of a subset of differentiation associated enhancers. [Nat Commun] Full Article

Despite Mutation Acquisition in Hematopoietic Stem Cells, JMML-Propagating Cells Are Not Always Restricted to This Compartment

Combining genomic, colony forming assay and xenograft studies, the authors detected the presence of juvenile myelomonocytic leukemia (JMML)-propagating cells that faithfully reproduced JMML features including the complex/nonlinear organization of dominant/minor clones, both at diagnosis and relapse. [Leukemia] Full Article

Liquid Biopsy for Minimal Residual Disease Detection in Leukemia Using a Portable Blast Cell Biochip

Investigators described a robust system for the simultaneous detection and enrichment of rare blast cells. Enrichment of blast cells was achieved from blood with a one-step microfluidic blast cell biochip sorting system, without specific targeting of proteins by antibodies. [npj Precis Oncol] Full Article

CLINICAL RESEARCH

Single-Cell Multiomic Analysis Identifies Regulatory Programs in Mixed-Phenotype Acute Leukemia

Researchers established a normal epigenetic baseline for healthy blood development, which they then used to deconvolve aberrant molecular features within blood from patients with mixed-phenotype acute leukemia. Despite widespread epigenetic heterogeneity within the patient cohort, they observed common malignant signatures across patients as well as patient-specific regulatory features that were shared across phenotypic compartments of individual patients. [Nat Biotechnol] Abstract

Mutations Associated With Age-Related Clonal Hematopoiesis in PMF Patients with Rapid Progression to Myelofibrosis

To determine the impact of age-related clonal hematopoiesis related mutations for development of fibrosis in primary myelofibrosis (PMF), the mutational status of cases with fibrotic progression from grade 0 to grade 2/3 as evidenced by follow-up bone marrow biopsies was compared with prefibrotic PMF samples without development of fibrosis. Frequent ARCH/CHIP-associated mutations demonstrable at presentation were not connected with fibrotic progression. [Leukemia] Abstract

Allogeneic Transplantation in Elderly Patients ≥65 Years with Non-Hodgkin Lymphoma: A Time-Trend Analysis

Using the CIBMTR registry, researchers report a time-trend analysis of 727 non-Hodgkin lymphoma patients undergoing the first allo-hematopoietic cell transplantation from 2000 to 2015 in the United States. Study cohorts were divided by time period: 2000–2005 vs. 2006–2010 vs. 2011–2015. Primary outcome was overall survival. Secondary outcomes included progression-free survival, relapse/progression, and non-relapse mortality. [Blood Cancer J] Full Article

Subscribe to one of our other 19 science newsletters such as Cord Blood News & Cell Therapy News.

Extramedullary Multiple Myeloma

Despite improvement in survival for most patients with multiple myeloma over recent decades, outcomes were generally poor when extramedullary multiple myeloma develops. Understanding the molecular underpinnings leading to homing of plasma cells in ecosystems outside the bone marrow will be crucial for therapeutically manipulating the micro-environment and targeting key signaling pathways. [Leukemia] Abstract

The Effect of Co-Occurring Lesions on Leukaemogenesis and Drug Response in T-ALL and ETP-ALL

The authors outline the genomic alterations that occur in T cell acute lymphoblastic leukaemia (ALL) and early T cell precursor (ETP)-ALL and review studies highlighting the possible effects of co-occurring lesions on leukaemogenesis and drug response. [Br J Cancer] Abstract

MicroRNAs in Graft-Versus-Host Disease: A Review of the Latest Data

Investigators summarize the current knowledge on the involvement of small RNAs in the pathophysiology of this disease. They also review studies investigating the potential of miRNAs as biomarkers for early detection, follow-up, and prognosis of graft-versus-host disease. [Bone Marrow Transplant] Abstract

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

Akari Therapeutics Announces Pivotal Phase III Trial Design of Nomacopan in Pediatric Hematopoietic Stem Cell Transplan–Related Thrombotic Microangiopathy (HSCT-TMA), Following FDA Meeting

Akari Therapeutics, Plc announced the design of a pivotal Phase III pediatric trial in HSCT-TMA following a FDA End-of-Phase II meeting. Akari also announces that, in another hematological condition, all six patients from the long-term Phase II PNH study who were transfusion dependent at entry are now transfusion independent on long-term treatment with nomacopan. [Akari Therapeutics, Plc] Press Release

Rafael Pharmaceuticals Announces Expansion of Phase II Trial of CPI-613^® (Devimistat) for Patients With Relapsed or Refractory Burkitt’s Lymphoma/Leukemia to Massachusetts General Hospital in Boston

Rafael Pharmaceuticals, Inc. announced the expansion of its Phase II clinical trial of CPI-613^® for patients with relapsed or refractory Burkitt’s lymphoma/leukemia. The clinical trial will begin enrolling patients at Massachusetts General Hospital in Boston starting this month. The trial is currently underway at Memorial Sloan Kettering Cancer Center in New York City and at City of Hope in Duarte, California. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

OSE Immunotherapeutics Announces Positive Results From Phase I Clinical Study of Anti-IL-7 Receptor Antagonist OSE-127

OSE Immunotherapeutics announced completion and positive results from the Phase study of OSE-127, a humanized monoclonal antibody with a differentiated mechanism of action as a full-antagonist of the CD127 receptor, the alpha chain of the interleukin-7 receptor. [OSE Immunotherapeutics] Press Release

Seattle Genetics Announces Health Canada Approval of ADCETRIS^® (Brentuximab Vedotin) in Combination With Chemotherapy in Frontline CD30-Expressing Peripheral T-Cell Lymphoma

Seattle Genetics, Inc. announced that Health Canada has approved the supplemental New Drug Submission that expands the use of ADCETRIS in combination with CHP chemotherapy for the treatment of previously untreated adult patients with systemic anaplastic large cell lymphoma, peripheral T-cell lymphoma-not otherwise specified or angioimmunoblastic T-cell lymphoma, whose tumors express CD30. [Seattle Genetics, Inc.] Press Release

Crack Down on Genomic Surveillance

Concerns about the potential downsides of governments being able to interrogate people’s DNA have been voiced since the early 2000s by activist groups, such as the non-profit organization GeneWatch UK, and some geneticists. [Nature News] Editorial

Elsevier Progresses in Open-Access Deal Making

The scholarly publisher has announced several new licensing agreements in both Europe and the US, but some major academic groups are still without contracts and access to journals. [The Scientist] Editorial

NEW Keystone Symposia: Noncoding RNAs – Mechanism, Function and Therapies
January 12-16, 2020
Whistler, British Columbia, Canada

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

NEW Postdoctoral Position – Oncogenic Events in Acute Lymphoblastic Leuemia (KU Leuven)

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

Department Director – Hematopathology (University of Vermont)

Postdoctoral Fellowships – Cancer Research (Harvard Medical School)

Postdoctoral Fellowship – Leukemia (Uniformed Services University of the Health Sciences)

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)

PhD Project – Physical Biology of Blood Stem Cells (University of York)

Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Hematopoiesis News? Click here to submit!

Comments or suggestions? Submit your feedback here.