Hematopoiesis News Volume 11.03 | Jan 28 2020

TOP STORY

Lineage Tracing on Transcriptional Landscapes Links State to Fate During Differentiation

The authors identified states of primed fate potential and located them on a continuous transcriptional landscape. They identified two routes of monocyte differentiation that left an imprint on mature cells. [Science] Abstract

(Ranked by impact factor of the journal)

β4GALT1 Controls β1 Integrin Function to Govern Thrombopoiesis and Hematopoietic Stem Cell Homeostasis

Researchers identified the conserved B4galt1 gene as a critical regulator of thrombopoiesis in megakaryocyte (MKs). β4GalT1 deficiency increased the number of fully differentiated MKs. However, the resulting lack of glycosylation enhances β1 integrin signaling leading to dysplastic MKs with severely impaired demarcation system formation and thrombopoiesis. [Nat Commun] Full Article

Targeting NAD Immunometabolism Limits Severe Graft-Versus-Host Disease and Has Potent Antileukemic Activity

The authors showed that nicotinamide phosphoribosyl-transferase (Nampt) blockage strongly ameliorated acute graft-versus-host disease (GVHD) and limited leukemic expansion. Nampt was highly elevated in serum of patients with gastrointestinal GVHD and was particularly abundant in human and mouse intestinal T cells. [Leukemia] Abstract | Press Release

Adult T-Cell Acute Lymphoblastic Leukemias with IL7R Pathway Mutations Are Slow-Responders Who Do Not Benefit From Allogeneic Stem-Cell Transplantation

Scientists performed a comprehensive study of 200 adult patients with T-cell acute lymphoblastic leukemia (T-ALL) included in the GRAALL2003/2005 protocols to address the clinical significance of IL7Rp mutations. Next-generation sequencing of the IL7Rp revealed that IL7Rp mutations were frequent in adult T-ALL, particularly in immature/early T-cell progenitor-ALL. [Leukemia] Abstract

The Significance of Genetic Mutations and Their Prognostic Impact on Patients with Incidental Finding of Isolated del(20q) in Bone Marrow without Morphologic Evidence of a Myeloid Neoplasm

To explore the potential risk stratification markers in this group of patients, the authors evaluated their genetic mutational landscape by a 35-gene myeloid neoplasm (MN)-focused next-generation sequencing panel and examined the association of mutations to progression of MNs. The study included 56 patients over a 10-year period with isolated del(20q), of whom 23 harbored at least one mutation. [Blood Cancer J] Full Article

Application of an Ex Vivo Drug Sensitivity Platform Towards Achieving Complete Remission in a Refractory T-Cell Lymphoma

Scientists developed an experimental-analytical hybrid method, Quadratic phenotypic optimization platform (QPOP), which ranked drug combinations using a limited amount of tumor2. QPOP identified optimal combinations based on the observation that biological response to perturbations could be mapped to a second-order polynomial equation. [Blood Cancer J] Full Article

Human Bone Marrow Is Comprised of Adipocytes with Specific Lipid Metabolism

The authors compared human primary bone marrow adipocytes (BM-Ads) did not decrease in size compared to white adipocytes, suggesting they harbored unique metabolic properti with paired subcutaneous adipocytes (SC-ADs) using proteomic and lipidomic approaches. They found that that, although SC-Ads and BM-Ads shared similar morphological features, they possessed distinct lipid metabolism. [Cell Rep] Full Article | Graphical Abstract

Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow

Researchers present an unexpected role of vitamind D receptor (VDR) in normal hematopoiesis and in leukemogenesis. Limited VDR expression is associated with impaired myeloid progenitor differentiation and is a new prognostic factor in acute myeloid leukemia. In mice, the lack of Vdr resulted in increased numbers of hematopoietic and leukemia stem cells and quiescent hematopoietic stem cells. [Cell Rep] Full Article

On-Chip Recapitulation of Clinical Bone Marrow Toxicities and Patient-Specific Pathophysiology

Investigators showed that a vascularized human bone marrow (BM)-on-a-chip supported the differentiation and maturation of multiple blood cell lineages over four weeks while improving CD34⁺ cell maintenance, and that it recapitulatef aspects of BM injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs and ionizing radiation, as well as BM recovery after drug-induced myelosuppression. [Nat Biomed Eng] Abstract

CLINICAL RESEARCH

Dose Escalation Prophylactic Donor Lymphocyte Infusion after T-Cell Depleted Matched Related Donor Allogeneic Hematopoietic Cell Transplantation Is Feasible and Results in Higher Donor Chimerism, Faster Immune Re-Constitution, and Prolonged Progression-free survival

Scientists conducted a prospective trial exploring the feasibility of early withdrawal of immunosuppression at day 60 followed by dose escalation of prophylactic donor lymphocyte infusion (pDLI) after alemtuzumab-based, T-cell depleted conditioning for patients with high-risk hematologic malignancies. pDLI were administered at day 75 to day 90 and again in four-eight week intervals with receipt of up to 5 pDLI infusions. [Bone Marrow Transplant] Abstract

Immune Profiles in Acute Myeloid Leukemia Bone Marrow Associate with Patient Age, T-Cell Receptor Clonality, and Survival

Researchers compared the immunologic landscape of formalin-fixed paraffin-embedded bone marrow trephine samples from acute myeloid leukemia (AML), chronic myeloid leukemia (AML), and B-cell acute lymphoblastic leukemia patients at diagnosis to controls with 30 immunophenotype markers using multiplex immunohistochemistry and computerized image analysis. They identified distinct immunologic profiles specific for leukemia subtypes and controls enabling accurate classification of AML, chronic myeloid leukemia, B-cell acute lymphoblastic leukemia, and control subjects [Blood Adv] Full Article | Graphical 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

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

HTG Molecular Diagnostics Receives European Patent Grant Notification for Methods for Subtyping Diffuse Large B-Cell Lymphoma

HTG Molecular Diagnostics, Inc. announced it has received notification of validation of European patent number EP 3356554 for its methods for subtyping diffuse large B-cell lymphoma, effective October 2019. HTG was previously granted a patent for this technology in the United States in 2018. [HTG Molecular Diagnostics, Inc.] Press Release

Feds Fund Innovative Health Research Happening at DAL, NSHA and IWK

Dalhousie University is home to four of the newest recipients of funding from the Government of Canada for their innovative health research. The $1,159,527 in funding is provided by the Canadian Institutes of Health Research Project Grants, which help researchers gather the kind of information they need to make real improvements to clinical practice, health service delivery, and public health policy. [Dalhousie University] Press Release

Top Harvard Chemist Charged with Lying about Ties to Chinese Government Program

The head of Harvard University’s chemistry department was charged with attempting to conceal his involvement in a Chinese government program to bring scientists to China, an escalation of a crackdown by US authorities on what they perceive as a campaign to steal ideas born in American universities and medical centers. [STAT News] Editorial

Iranian Students Denied Entry to US

Despite having valid visas to attend universities, more than a dozen would-be graduate students have been detained at the airport and sent back to Iran in recent months. [The Scientist] Editorial

Brazil’s Pick of a Creationist to Lead Its Higher Education Agency Rattles Scientists

The appointment of a creationism advocate to lead the agency that oversees Brazil’s graduate study programs has scientists there concerned-yet again-about the encroachment of religion on science and education policy. President Jair Bolsonaro’s administration on Saturday January 25^th named Benedito Guimarães Aguiar Neto to head the agency, known as CAPES, who previously served as the rector for a private religious school which advocates the teaching and study of intelligent design. [ScienceInsider] Editorial

NEW The Evolving Landscape of Cancer Modeling
March 2-5, 2020
San Diego, California, United States

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

NEW Medical Technologist – Blood Bank (The University of Texas MD Anderson Cancer Center)

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

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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