Hematopoiesis News Volume 10.04 | Feb 5 2019

TOP STORY

AIBP-Mediated Cholesterol Efflux Instructs Hematopoietic Stem and Progenitor Cell Fate

AIBP-mediated cholesterol efflux activated endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivated Notch and promoted hematopoietic stem and progenitor cell (HSPC) emergence. Srebp2 inhibition impaired hypercholesterolemia-induced HSPC expansion. [Science] Abstract

(Ranked by impact factor of the journal)

Acute Myeloid Leukemia Induces Protumoral p16INK4a-Driven Senescence in the Bone Marrow Microenvironment

Scientists report that acute myeloid leukemia (AML) blasts induced a senescent phenotype in the stromal cells within the bone marrow (BM) microenvironment and that the BM stromal cell senescence was driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feed back to promote AML blast survival and proliferation via the senescence-associated secretory phenotype. [Blood] Abstract | Press Release | Graphical Abstract

MHC Class II Cell-Autonomously Regulates Self-Renewal and Differentiation of Normal and Malignant B Cells

Major histocompatibility complex class II (MHC II) deficiency preserved stem cell characteristics in developing pro-B cells in vivo and ectopic MHC II expression accelerated HSC differentiation in vitro. Moreover, MHC II expression restrained growth of murine B cell leukaemia cell lines in vitro and in vivo, independently of CD4⁺ T cell surveillance. [Blood] Abstract

A Novel Method for Detecting the Cellular Stemness State in Normal and Leukemic Human Hematopoietic Cells Can Predict Disease Outcome and Drug Sensitivity

Using a novel reporter, scientists revealed cellular heterogeneity in several leukemia cell lines and patient-derived samples. Alterations in reporter activity were associated with transcriptomic and functional changes that were closely related to the HSC identity. [Leukemia] Abstract

The NUP98-HOXD13 Fusion Oncogene Induces Thymocyte Self-Renewal via Lmo2/Lyl1

Scientists find that thymocytes from preleukemic NUP98-HOXD13-transgenic (NHD13-Tg) mice can serially transplant, demonstrating that they have self-renewal capacity. Transcriptome analysis showed that NHD13-Tg thymocytes exhibited a stem cell-like transcriptional program closely resembling that induced by Lmo2, including Lmo2 itself and its critical cofactor Lyl1. [Leukemia] Abstract

Genetically Modified Hematopoietic Stem/Progenitor Cells that Produce IL-10-Secreting Regulatory T Cells

Four previously described Vα3.2 Vβ14 T cell receptor cDNAs, the dominant clonotype generated in splenocytes after immunization of SJL mice, that differed only in their CDR3 sequences were utilized to generate retrogenic mice. [Proc Natl Acad Sci USA] Abstract

Age-Related Differences in the Bone Marrow Stem Cell Niche Generate Specialized Microenvironments for the Distinct Regulation of Normal Hematopoietic and Leukemia Stem Cells

In vivo self-renewal of leukemia stem cells was higher in adult bone marrow (BM) than in neonatal BM, with increased frequencies of leukemia-initiating cells as well as higher lympho-myeloid differentiation potential towards biphenotypic leukemic cells. [Sci Rep] Full Article

CLINICAL RESEARCH

Hematopoietic Stem-Cell Transplantation in Children with Refractory Acute Myeloid Leukemia

Data was collected through the nation-wide registry program in Japan. A total of 417 acute myeloid leukemia patients 20 years or younger at HSC transplantation, between January 2001 and December 2015, were included. A total of 314 patients died, and the median follow-up duration of the survivors was 1052 days. The most frequent cause of death was leukemia progression. [Bone Marrow Transplant] Abstract

Unmanipulated Haploidentical versus HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Acute Myeloid Leukemia: A Retrospective Study on Behalf of the ALWP of the EBMT

The authors compared outcomes of hematopoietic stem-cell transplantation from HLA-identical sibling or haploidentical donors in patients with refractory or relapsed acute myeloid leukemia, performed during the period 2007–2015. [Bone Marrow Transplant] Abstract

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

Rethinking Clinical Trial Endpoints in Myelodysplastic Syndromes

The authors review challenges in drug development in myelodysplastic syndromes with respect to aligning trial endpoints for lower and higher risk patients with treatment goals meaningful to patients. [Leukemia] Abstract

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

MaaT Pharma Announces Positive DSMB Safety Review and Continuation of its Phase II HERACLES Study in Acute GvHD

MaaT Pharma announced that its independent Data and Safety Monitoring Board (DSMB) completed its first safety assessment of the company’s ongoing Phase II HERACLES study with lead biotherapeutic MaaT013 in steroid-resistant, gastrointestinal-predominant, acute Graft-versus-Host-Disease (GvHD) after allogeneic hematopoietic stem-cell transplantation. [MaaT Pharma] Press Release

Syntrix Wins $3.4M NIH Grant to Conduct Phase I/II Trial of SX-682 in Myelodysplastic Syndrome

Syntrix Pharmaceuticals announced that it has been awarded a three-year grant worth $3.4 million from the National Heart Lung and Blood Institute of the National Institutes of Health (NIH) to assess its investigational CXCR1/2 inhibitor SX-682 in patients with low- and high-risk myelodysplastic syndrome who had progression or were intolerant to prior therapy. [Syntrix Pharmaceuticals (PR Newswire Association LLC.)] Press Release

Cellect Begins Collaboration with Washington University in Preparation for First U.S. Clinical Trial Using Cellect’s ApoGraft™ for Bone Marrow Transplantations

Cellect Biotechnology Ltd. announced a collaboration with Washington University, a leading academic institution based in St. Louis, MO, aimed at determining the safety and tolerability in a U.S. Phase I/II study using ApoGraft™ for bone marrow transplantations. [Cellect Biotechnology Ltd. (PR Newswire Association LLC.)] Press Release

Actinium Initiates Novel Phase I/II Combination Trial of Actimab-A and Venetoclax

Actinium Pharmaceuticals, Inc. announced that its novel Phase I/II combination trial of Actimab-A and venetoclax has been initiated. [Actinium Pharmaceuticals, Inc.] Press Release

Stemline Therapeutics Announces Validation of Marketing Authorization Application (MAA) by the European Medicines Agency (EMA)

Stemline Therapeutics, Inc. announced that the EMA has completed its validation of the MAAA for ELZONRIS^™. Stemline submitted the MAA seeking approval of ELZONRIS for the treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm. In November 2018, the MAA was granted accelerated assessment. [Stemline Therapeutics, Inc.] Press Release

Thousands of Scientists Run Up against Elsevier’s Paywall

Researchers at German institutions that have let their Elsevier subscriptions lapse while negotiating a new deal are hitting the paywall for the publisher’s most recent articles around 10,000 times a day, according to Elsevier — which publishes more than 400,000 papers each year. [Nature News] Editorial

After Shutdown, NSF Catching Up on Review Panels, Funding Requests

When the US government was partially shut down for 35 days starting December 22, work at several government agencies ground to a halt, with a total of 800,000 federal employees furloughed. The National Science Foundation (NSF), one of the sidelined science agencies, is now addressing all that went undone during that time, NSF officials told reporters. [The Scientist] Editorial

Rookies Lead the Way on House Science Panel

A major perk of being the majority party in the U.S. Congress is getting to fill the leadership slots on every committee. For several new Democratic legislators, however, having their party regain control of the House of Representatives also creates an unprecedented opportunity to shape U.S. science policy. [ScienceInsider] Editorial

Indian Government to Boost Stipend for Early-Career Scientists

The Indian government announced that it will increase the stipend for PhD students who have qualified for a research fellowship by up to 25%. [Nature News] Editorial

NEW 2^nd Annual Meeting of the American Society for Gene & Cell Therapy (ASGCT)
April 29-May 2, 2019
Washington, DC, United States

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

NEW Chair – Microbiology and Immunology (Indiana University School of Medicine)

Postdoctoral Studies – Normal & Malignant Hematopoiesis (Karolinska Institutet)

Investigator Positions – Hematologic Malignancies (University of Alabama Birmingham)

Postdoctoral Associate – T-ALL Research (University of New Mexico)

Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University)

Postdoctoral Research Scholar – Hematologic Malignancies (Washington University School of Medicine)

Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine)

Postdoctoral Fellowship – Leukemic & Normal Stem Cell Biology (Indiana University School of Medicine)

Assistant Project Scientist – Hematology and Oncology (University of California, Davis)

Faculty Positions – Hematology and Oncology (University of California, Davis)

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.