Hematopoiesis News Volume 9.29 | Jul 24 2018

TOP STORY

Leukemia Hijacks a Neural Mechanism to Invade the Central Nervous System

Investigators showed that acute lymphoblastic leukemia cells in circulation are unable to breach the blood-brain barrier in mice; instead, they migrate into the central nervous system along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Domain-Focused CRISPR Screen Identifies HRI as a Fetal Hemoglobin Regulator in Human Erythroid Cells

Increasing fetal hemoglobin (HbF) levels in adult red blood cells provides clinical benefit to patients with sickle cell disease and some forms of β-thalassemia. To identify potentially druggable HbF regulators in adult human erythroid cells, scientists employed a protein kinase domain-focused CRISPR-Cas9-based genetic screen with a newly optimized single-guide RNA scaffold. [Science] Abstract | Press Release

Oncogenic Hijacking of the Stress Response Machinery in T Cell Acute Lymphoblastic Leukemia

Researchers showed that the expression of heat shock transcription factor 1 (HSF1) and the downstream mediators of the heat shock response were transcriptionally upregulated in T cell acute lymphoblastic leukemia (T-ALL). Hsf1 ablation suppressed the growth of human T-ALL and eradicated leukemia in mouse models of T-ALL, while sparing normal hematopoiesis. [Nat Med] Abstract | Press release

Single Cell Approaches Identify the Molecular Network Driving Malignant Hematopoietic Stem Cell Self-Renewal

Single cell gene expression and functional assays identified a subset of JAK2V617F mutant HSCs that displayed defective self-renewal. This defect was rescued at the single HSC level by crossing JAK2V617F mice with mice lacking TET2, the most commonly co-mutated gene in myeloproliferative neoplasm patients. [Blood] Abstract

Lineage Marker Synchrony in Hematopoietic Genealogies Refutes the PU.1/GATA1 Toggle Switch Paradigm

The authors presented a computational method to infer decision time points from correlated marker signals in genealogies and applied it to differentiating hematopoietic stem cells. They found that myeloid lineage decisions happen generations before lineage marker onsets. [Nat Commun] Full Article

Identification of Immune-Activated Hematopoietic Stem Cells

Researchers employed the Fgd5^mCherry reporter mouse to improve identification of activated HSCs. [Leukemia] Full Article

Niche TWIST1 Is Critical for Maintaining Normal Hematopoiesis and Impeding Leukemia Progression

Using a chimeric mice model, researchers demonstrated that Twist1 deletion in the microenvironment resulted in alteration of multiple niche cells as well as downregulated expression of major hematopoietic stem cell supportive factors. The perturbed microenvironment reduced hematopoietic stem cell homing and retention, impaired hematopoietic stem cell self-renewal and induced myeloid skewing. [Haematologica] Abstract | Full Article

Microfluidics-Based Super-Resolution Microscopy Enables Nanoscopic Characterization of Blood Stem Cell Rolling

Investigators introduced a microfluidics-based super-resolution fluorescence imaging platform and applied the method to investigate the initial essential step in the homing, tethering, and rolling of hematopoietic stem/progenitor cells (HSPCs) under external shear stress that is mediated by selectins, expressed on endothelium, with selectin ligands expressed on HSPCs. [Sci Adv] Full Article

CLINICAL RESEARCH

CPX-351 (Cytarabine and Daunorubicin) Liposome for Injection versus Conventional Cytarabine plus Daunorubicin in Older Patients with Newly Diagnosed Secondary Acute Myeloid Leukemia

In this open-label, randomized, Phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. [J Clin Oncol] Full Article | Press Release

Acute Lymphoblastic Leukemia as a Clonally Unrelated Second Primary Malignancy after Multiple Myeloma

Scientists report 13 cases of B-cell acute lymphoblastic leukemia (ALL) following therapy for multiple myeloma (MM). MM therapy included immunomodulatory agents in all patients and autologous hematopoietic cell transplantation in ten patients preceding ALL diagnosis. Analysis of paired samples of MM and ALL using whole exome sequencing demonstrated that the malignancies arose from different clones. [Leukemia] Abstract

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

Molecular Remission as a Therapeutic Objective in Acute Promyelocytic Leukemia

Following early retrospective studies indicating the prognostic relevance of PML/RARA monitoring, several prospective studies were conducted in large cohorts of acute promyelocytic leukemia patients enrolled in clinical trials with the aim of better assessing the prognostic value of longitudinal PCR testing. [Leukemia] Abstract

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

UC San Diego Researchers Receive Funding to Pursue Novel Stem Cell-Based Treatments

The governing board of the California Institute for Regenerative Medicine (CIRM) unanimously approved this week two grants worth more than $2.2 million to University of California San Diego School of Medicine researchers investigating stem cell-based therapies for a rare genetic disorder that affects the heart and a chronic, progressive affliction of the lungs. [University of California, San Diego] Press Release

Tolero Pharmaceuticals Advances Investigational Agent Alvocidib into Second Stage of Phase II Zella 201 Study in Patients with Relapsed Refractory MCL-1-Dependent AML

Tolero Pharmaceuticals, Inc. announced that it has initiated the second stage of the Phase II Zella 201 study evaluating the efficacy and safety of alvocidib, a potent CDK9 inhibitor, in combination with cytarabine and mitoxantrone in patients with relapsed or refractory MCL-1-dependent acute myeloid leukemia (AML). [Tolero Pharmaceuticals, Inc.] Press Release

Cellectar Reports Positive Phase II Interim Data for CLR 131 in Relapsed/Refractory DLBCL Patients

Cellectar Biosciences announced positive interim results from the company’s Phase II clinical trial for its lead product candidate CLR 131, in patients with diffuse large B-cell lymphoma (DLBCL). [Cellectar Biosciences] Press Release

FDA Grants Approval of TIBSOVO^®, the First Oral, Targeted Therapy for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia and an IDH1 Mutation

Agios Pharmaceuticals, Inc. announced that TIBSOVO^® was granted approval from the US FDA for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA approved test. [Agios, Inc.] Press Release

SELLAS Receives Fast Track Designation from FDA for Galinpepimut-S for the Treatment of Patients with Multiple Myeloma

SELLAS Life Sciences Group Inc. announced that the US FDA has granted Fast Track designation to the company’s lead asset, galinpepimut-S, for the treatment of multiple myeloma. [SELLAS Life Sciences Group Inc.] Press Release

NIH Delays Controversial Clinical Trials Policy for Some Studies

Basic brain and behavioral researchers will get more than a year to comply with a new U.S. policy that will treat many of their studies as clinical trials. The announcement from the National Institutes of Health (NIH) appears to defuse, for now, a yearlong controversy over whether basic research on humans should follow the same rules as studies testing drugs. [ScienceInsider] Editorial

University of Edinburgh Demands Retraction of Researcher’s Papers

The University of Edinburgh has asked for the retraction of five papers by cell biologist and former faculty member Irina Stancheva following an internal investigation into scientific misconduct allegations, according to Times Higher Education. [The Scientist] Editorial

NEW 2^nd How to Diagnose & Treat Multiple Myeloma
April 5-7, 2019
Berlin, Germany

NEW 5^th International Conference on Acute Myeloid Leukemia “Molecular & Translational” Advances in Biology & Treatment
October 24-26, 2019
Estoril, Portugal

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

NEW Research Technicians – Hematopoiesis (Fred Hutchinson Cancer Research Center)

NEW Research Assistant – Stem Cell Biology (NUI Galway)

NEW Postdoctoral Researcher – Stem Cell Biology (NUI Galway)

NEW Postdoctoral Scientist – Leukemia Biology (Nuffield Division of Clinical Laboratory Sciences, University of Oxford)

Research Technologist – Hematopoietic (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Hematopoiesis (Fred Hutchinson Cancer Research Center)

Endowed Chair – Cancer Research (University of Iowa Health Care)

Postdoctoral Research Fellows – Tissue Morphogenesis (Max-Planck-Institute for Molecular Biomedicine)

Career Development Program – Glycoscience (BloodCenter of Wisconsin)

Research Fellow – Stem Cell Biology & Engineering (New York Blood Center)

Postdoctoral Researcher – Regulation of Normal and Malignant Hematopoiesis (Karolinska Institutet)

Postdoctoral Position – Hematopoietic and Induced Pluripotent Stem Cells (Indiana University School of Medicine)

Postdoctoral Research Associate – Mechanisms of Leukemia (University of Virginia)

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.