Hematopoiesis News Volume 10.30 | Aug 6 2019

TOP STORY

Therapeutically Relevant Engraftment of a CRISPR-Cas9-Edited HSC-Enriched Population with HbF Reactivation in Nonhuman Primates

Researchers evaluated the therapeutic potential of hematopoietic stem and progenitor cells edited with the CRISPR-Cas9 nuclease platform to recapitulate naturally occurring mutations identified in individuals who expressed increased amounts of fetal hemoglobin (HbF), a condition known as hereditary persistence of HbF. [Sci Transl Med] Abstract | Press Release | Editorial

(Ranked by impact factor of the journal)

Phc2 Controls Hematopoietic Stem and Progenitor Cell Mobilization from Bone Marrow by Repressing Vcam1 Expression

The genetic ablation of Phc2 in mice caused a severe defect in hematopoietic stem and progenitor cell mobilization through the derepression of Vcam1 in bone marrow stromal cells, ultimately leading to a systemic immunodeficiency. [Nat Commun] Full Article

A Three-Dimensional In Vitro Model of Erythropoiesis Recapitulates Erythroid Failure in Myelodysplastic Syndromes

Scientists developed an efficient and robust 3D scaffold culture model supporting terminal erythroid differentiation from both mononuclear or CD34⁺-enriched primary bone marrow cells from healthy donors and myelodysplastic syndrome with ring sideroblasts patients. [Leukemia] Full Article

Combined Inhibition of MDM2 and Bcr-Abl Tyrosine Kinase Targets Chronic Myeloid Leukemia Stem/Progenitor Cells in a Murine Model

Combined inhibition of BCR-ABL1 with imatinib and MDM2 with DS-5272 increased NOXA level, markedly reduced leukemic linage-SCA-1+C-KIT+ cells and hematopoiesis, decreased leukemia burden, significantly prolonged the survival of mice engrafted with bone marrow cells from Scl-tTa-BCR-ABL1 mice, and significantly decreased chronic myeloid leukemia stem cell frequency in secondary transplantations. [Haematologica] Abstract | Full Article

Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia

Using a conditional mouse model where zinc-finger transcription factor Gata2 was deleted specifically in hematopoietic cells, investigators showed that knockout of Gata2 led to rapid and complete cell-autonomous loss of adult HSC. [Stem Cell Reports] Full Article | Graphical Abstract

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature

To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, researchers investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen-matched related or unrelated donor stem cell transplantation (SCT), or autologous SCT. [Cancers] Full Article

Fetal Liver Mll-AF4⁺ Hematopoietic Stem and Progenitor Cells Respond Directly to poly(I:C), but Not to a Single Maternal Immune Activation

Scientists used the Mll-AF4 pre-leukemia mouse model that initiated the expression of Mll-AF4 in the first definitive hematopoietic cells formed during embryonic development. They observed an increase in proliferation upon hematopoietic differentiation of fetal liver Mll-AF4⁺ LSK exposed to the immune stimulants poly(I:C) or LPS/lipopolysaccharide. [Exp Hematol] Full Article

CLINICAL RESEARCH

Myeloid Neoplasms in the Setting of Sickle Cell Disease: An Intrinsic Association with the Underlying Condition Rather than a Coincidence; Report of 4 Cases and Review of the Literature

Scientists retrospectively analyzed 4 cases of sickle cell disease patients who developed myeloid neoplasm. Age at time of diagnosis ranged from 27 to 59 years with a median of 35.5 years. Two patients were treated with hydroxyurea and the other 2 with supportive care alone, with 1 out of the 4 patients receiving additional treatment with HSC transplant. [Mod Pathol] Abstract

Anti-CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy Bridging to Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: An Open-Label Pragmatic Clinical Trial

Investigators explored whether consolidative allogeneic HSC transplantation could improve the long-term prognosis of the minimal residual disease-negative complete remission patients after chimeric antigen receptor-modified T-cell therapy. [Am J Hematol] Abstract

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Which Are the Most Promising Targets for Minimal Residual Disease-Directed Therapy in Acute Myeloid Leukemia Prior to Allogeneic Stem Cell Transplant?

The authors review promising targets of minimal residual disease prior to allogeneic stem cell transplantation. Specifically, they focus on the rationale and clinical development of therapies targeting oncogenic driver mutations, apoptosis, methylation, and leukemic immune targets. [Haematologica] Full Article

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

Oncternal Therapeutics Announces Opening of Randomized Phase II Study of Cirmtuzumab in Combination with Ibrutinib

Oncternal Therapeutics, Inc. announced that it has opened for enrollment its randomized Phase II study of cirmtuzumab, a ROR1-targeted monoclonal antibody, combined with ibrutinib in patients with chronic lymphocytic leukemia. [Oncternal Therapeutics, Inc. (GlobeNewswire, Inc.)] Press Release

FDA Clears IND for Mustang Bio’s MB-102 (CD123 CAR T)

Mustang Bio, Inc. announced that the FDA has approved the company’s Investigational New Drug (IND) application to initiate a multi-center Phase I/II clinical trial of MB-102 in acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm and high-risk myelodysplastic syndrome. [Mustang Bio, Inc.] Press Release

Rafael Pharmaceuticals Announces Expansion into Austria, South Korea and Spain of Pivotal Phase III Trial (ARMADA 2000) of CPI-613^® (Devimistat) in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)

Rafael Pharmaceuticals, Inc. announced the expansion of its Phase III clinical trial of devimistat in patients with relapsed or refractory AML into Austria, South Korea and Spain. The multicenter, open-label, randomized pivotal trial is evaluating the efficacy and safety of its lead compound devimistat in combination with high dose cytarabine and mitoxantrone in older patients with relapsed or refractory AML. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

Momenta Pharmaceuticals Launches Phase II/III Trial of M281 for the Treatment of Warm Autoimmune Hemolytic Anemia and Is Granted FDA Fast Track Designation

Momenta Pharmaceuticals, Inc. announced the launch of an adaptive Phase II/III clinical study for its FcRn inhibitor nipocalimab (M281) in warm autoimmune hemolytic anemia. This follows the acceptance of its Investigational New Drug application by the FDA. [Momenta Pharmaceuticals, Inc.] Press Release

Forty Seven, Inc. Announces $6 Million in Funding from the Leukemia & Lymphoma Society TAP to Accelerate the Development of 5F9 in Myelodysplastic Syndrome

Forty Seven, Inc. announced additional funding commitments from the Leukemia & Lymphoma Society, aimed at accelerating the development of 5F9 for the treatment of myelodysplastic syndromes. [Forty Seven, Inc.] Press Release

The Public’s Trust in Scientists Rises, Pew Poll Shows

Public trust in science rose in recent years, a new survey shows: 86 percent of Americans say that they have at least “a fair amount” of confidence in scientists to act in the public interest, up from 78 percent in 2016. [The Scientist] Editorial

First Human-Monkey Chimeras Developed in China

Juan Carlos Izpisúa Belmonte of the Salk Institute in San Diego is spearheading the project with scientists from his own lab and those from the Murcia Catholic University in Murcia, Spain. The team wants to develop chimeras—organisms composed of cells from two or more species—capable of growing human organs. [The Scientist] Editorial

NEW European Cancer Summit (ECCO) 2019
September 12-14, 2019
Brussels, Belgium

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

NEW Postdoctoral Positions – Stem Cell Biology, Cancer Biology, and Epigenetics (Baylor College of Medicine)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

PhD Position – Epigenetic Heterogeneity and Dynamics in Acute Myeloid Leukemia (University of Newcastle)

Postdoctoral Position – Advanced Proteomics & Erythropoiesis (Lund University)

Postdoctoral Fellow – Acute Myeloid Leukemia Research (University of Gothenburg)

Faculty Positions – Center for Childhood Cancer and Blood Diseases (The Research Institute at Nationwide Children’s Hospital)

Senior Scientist – Immuno-Oncology of Hematologic Malignancies (University of Kansas School of Medicine)

Postdoctoral Position – Hematopoietic Stem Cell Biology (Columbia University Irving Medical Center)

Postdoctoral Position – Leukemia Research (University of California, San Francisco)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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