Hematopoiesis News Volume 10.17 | May 7 2019

TOP STORY

Stage-Specific Requirement for Mettl3-Dependent m⁶A mRNA Methylation during Hematopoietic Stem Cell Differentiation

Researchers showed that deletion of the N⁶-methyladenosine (m⁶A) methyltransferase Mettl3 from the adult hematopoietic system led to an accumulation of HSCs in the bone marrow and a marked reduction of reconstitution potential due to a blockage of HSC differentiation. Deleting Mettl3 from myeloid cells using Lysm–cre did not impact myeloid cell number or function. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

Bone Marrow Dendritic Cells Regulate Hematopoietic Stem/Progenitor Cell Trafficking

Ablation of conventional dendritic cells (cDCs) resulted in hematopoietic stem/progenitor cell (HSPC) mobilization that was greater than that seen with ablation of bone marrow macrophages, and cDC ablation also synergized with G-CSF to mobilize HSPCs. Ablation of cDCs was associated with an expansion of bone marrow endothelial cells and increased vascular permeability. [J Clin Invest] Abstract | Full Article | Graphical Abstract

Clonal Evolution Patterns in Acute Myeloid Leukemia with NPM1 Mutation

To characterize the genetic composition of Nucleophosmin 1 (NPM1) mutated (NPM1^mut) acute myeloid leukemia, the authors assessed mutation status of five recurrently mutated oncogenes in 129 paired NPM1^mut samples obtained at diagnosis and relapse. They found a substantial shift in the genetic pattern from diagnosis to relapse including NPM1^mut loss. [Nat Commun] Full Article

Multilayer Intraclonal Heterogeneity in Chronic Myelomonocytic Leukemia

Investigators reprogrammed CD34-positive cells collected from a patient with a chronic myelomonocytic leukemia in which whole exome sequencing of peripheral blood monocyte DNA had identified 12 gene mutations, including a mutation in KDM6A and two heterozygous mutations in TET2 in the founding clone and a secondary KRASG12D mutation. Hematopoietic differentiation of these clones recapitulated the main features of the patient disease, including overproduction of granulomonocytes and dysmegakaryopoiesis. [Haematologica] Full Article

The Myeloid Differentiation Factor 88 Signaling in Donor T Cells Accelerates Graft-versus-Host Disease

While myeloid differentiation factor 88-deficient and wild-type T cells proliferated equivalently after transplantation, myeloid differentiation factor 88-deficient T cells demonstrated impaired survival and differentiation toward Th1, Tc1, and Th17, and induced less severe graft-versus-host disease compared to wild-type T cells. [Haematologica] Full Article

A 3D Atlas of Hematopoietic Stem and Progenitor Cell Expansion by Multi-Dimensional RNA-Seq Analysis

Combinatorial expression profiling revealed that, in the caudal hematopoietic tissue niche, hematopoietic stem and progenitor cells (HSPCs) and their neighboring supporting cells were co-regulated by shared signaling pathways and intrinsic factors, such as integrin signaling and Smchd1. Moreover, single-cell RNA-sequencing analysis unveiled the strong association between cell cycle status and HSPC differentiation. [Cell Rep] Full Article | Graphical Abstract

Acute Myeloid Leukemia Niche Regulates Response to L-Asparaginase

Scientists explored the susceptibility of acute myeloid leukemia-leukemic stem cells to anti-leukemic effect of L-asparaginase as well as the role of the two major cell types that constitute the bone marrow microenvironment, i.e., mesenchymal stromal cells and monocytes/macrophages. [Br J Haematol] Abstract | Full Article

Hemopoietic Cell Kinase Amplification with Protein Tyrosine Phosphatase Receptor T Depletion Leads to Polycythemia, Aberrant Marrow Erythoid Maturation, and Splenomegaly

Retroviral transduction of hemopoietic cell kinase into protein tyrosine phosphatase receptor T-null murine LKS⁺ stem and progenitor cells resulted in hyperproliferation in colony forming assays and hyperphosphorylation of intracellular STAT3. Furthermore, over half of the murine recipients of these transduced cells developed erythroid hyperplasia, polycythemia and splenomegaly at 12 months, although no leukemic phenotype was observed. [Sci Rep] Full Article

CLINICAL RESEARCH

Benzo[a]pyrene Is Associated with Dysregulated Myelo-Lymphoid Hematopoiesis in Asthmatic Children

Benzo[a]pyrene (B[a]P) was positively correlated with an increased expression of a heme biosynthesis gene, ALAS2, which in turn, appeared to promote concurrent increase of neutrophilic metamyelocyte and mature CD71^low erythroid cells. Furthermore, erythroid-specific master transcription regulator gene, glutathione transferase genes and eosinophil marker were simultaneously activated in the urban asthma cases. [Environ Int] Full Article

Risk Stratification and Prognosticators of Acute Myeloid Leukemia with Myelodysplasia-Related Changes Patients Undergoing Allogeneic Stem Cell Transplantation: A Retrospective Study of the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Transplantation outcomes of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) were compared with those of AML-not otherwise specified (AML-NOS) in patients who underwent allogeneic stem cell transplantation between 2003 and 2016 using a nationwide registration database. The three-year overall survival was lower and the relapse and non-relapse mortality rates were higher in the AML-MRC group than in the AML-NOS group. [Biol Blood Marrow Transplant] Abstract | Graphical Abstract

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New Insights into the Differentiation of Megakaryocytes from Hematopoietic Progenitors

The authors reexamine the canonical dogmas of megakaryopoiesis and provide an updated framework for interpreting the roles of traditional pathways in the context of new megakaryocyte biology. [Arterioscler Thromb Vasc Biol] Abstract

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

Takeda Expands Oncology Research, Demonstrating Commitment to Patient Community

Takeda Pharmaceutical Company Limited announced that it will present a total of five company-sponsored poster presentations, as well as an oral pipeline symposium. [Press release from Takeda Pharmaceutical Company Limited (Business Wire, Inc.) discussing research to be presented at the 15^th International Symposium on Myelodysplastic Syndromes, Copenhagen] Press Release

Onconova Therapeutics Announces Presentations

Onconova Therapeutics, Inc. announced that five posters related to the company’s lead product candidate, rigosertib, were accepted for presentation. [Press release from Onconova Therapeutics, Inc. discussing research to be presented at the 15^th International Symposium on Myelodysplastic Syndromes, Copenhagen] Press Release

Sigilon Therapeutics Delivers Oral Presentation on SIG-001 for Hemophilia A

Sigilon Therapeutics delivered an oral presentation featuring data on its hemophilia A program (SIG-001). The data presented will support the company’s planned regulatory filing of SIG-001 later this year to enable initiation of clinical trials. [Press release from Sigilon Therapeutics, Inc. discussing research presented at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, Washington, DC] Press Release

Moleculin Announces Additional Positive Interim Results in First Cohort of Phase I/II Clinical Studies of Annamycin in Acute Myeloid Leukemia in Europe

Moleculin Biotech, Inc. announced additional positive interim safety and efficacy data from its ongoing open label, single arm Phase I/II study of Annamycin in Poland. After receiving a single starting dose of 120 mg/m² in the first cohort of the dose escalation phase of the trial, two of three patients treated responded sufficiently to qualify for a potentially curative bone marrow transplant. [Moleculin Biotech, Inc.] Press Release

Agios Announces FDA Approval of Supplemental New Drug Application (sNDA) for TIBSOVO^® as Monotherapy for Newly Diagnosed Adult Patients with IDH1 Mutant Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy

Agios Pharmaceuticals, Inc. announced the FDA approved a sNDA to update the US prescribing information for TIBSOVO^® to include adult patients with newly diagnosed AML with a susceptible IDH1 mutation as detected by an FDA-approved test who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy. [Agios Pharmaceuticals, Inc.] Press Release

Black Academics Publish One-Fifth of South Africa’s Research

The proportion of scientific articles published by academics in South Africa who are black, colored or of Indian origin has risen almost tenfold since the end of apartheid, to about one-third, finds a report on scholarly publishing in the country. [Nature News] Editorial

White House to Convene Committee to Address Research Obstacles

The leaders of the White House Office of Science and Technology, National Institutes of Health, National Science Foundation, National Institute of Standards and Technology, and the Department of Energy’s science division have formed a committee “to address issues facing the US research community,” President Donald Trump’s administration announced. [The Scientist] Editorial

NEW European Society for Medical Oncology (ESMO) 2019 Congress
September 27-October 1, 2019
Barcelona, Spain

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

NEW Postdoctoral Research Fellow – Translational Gene Therapy & Hematopoietic Stem Cell Research (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Stem Cell Transplantation Cell Interaction (University of Illinois at Chicago)

Assistant Professor – Lymphoma/Myeloma Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Researcher – Stem Cells & Erythropoiesis in MDS (Karolinska Institutet)

Tenure Track Senior Investigator – Malignant Hematology (Northwestern University Feinberg School of Medicine)

Postdoctoral Fellows – Hematological Malignancies & Cancer Immunology (Fox Chase Cancer Center)

Postdoctoral Fellowship – Myeloma Research (University of Calgary)

Postdoctoral Position – Transcriptional Regulation in Leukemia (VIB KU Leuven)

Postdoctoral Fellow – Leukemia Cell Survival (City of Hope)

Postdoctoral Fellowship – Hematopoiesis, Leukemia & Bone Marrow Failure Syndromes (The University of Texas Southwestern)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

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