Volume 1, Issue 27


Cover Image

Cover Figure: Newly identified HSC-derived marrow endosteal cell (red cells) characterized as CD45-F4/80lo residing amongst osteoblasts in murine bone marrow. See the article by Overholt et al.

WASHINGTON, December 26,  2017 – Welcome to the “Advance Notice,”  newsletter which provides highlights from issues of Blood Advances, the open-access journal of the American Society of Hematology (ASH), that  are hand-picked by Blood Advances Editor-in-Chief Robert Negrin, MD.

Innate lymphoid cells have profound biological effects, and much more is yet to be learned about their origin, differentiation, and function in different situations. Raykova et al investigated the ability of type 3 innate lymphoid cells (ILC3s) to differentiate into natural killer cells through the stimulation of cytokines, including interleukins 12 and 15. This study points the way to mechanisms to harness the biological activity of ILC3s.

Loss-of-function mutations in the signaling protein tumor necrosis factor receptor–associated factor 3 (TRAF-3) are commonly found in many B-cell malignancies. Bangalore-Prakash and colleagues explore the relationship between the expression of the Epstein-Barr virus (EBV) oncoprotein LMP1 and sequestration of TRAF-3, highlighting this potential mechanism of EBV-related oncogenesis.

There is much interest in developing novel therapeutics and treatment strategies for patients with sickle cell disease (SCD). Standardization of responses would aid in the assessment of these different approaches over different studies and patient populations. In the article by Eckman and colleagues, leading experts in the treatment of SCD offer the PhenX Toolkit to recommend standard measures for use in clinical, epidemiological, and genomic studies.

The relationship between different clotting factors during the initiation of coagulation is an area of ongoing research. Wood and colleagues explore the interaction between factors Va and Xa with tissue factor pathway inhibitor α in detail with important findings in this critical coagulation mechanism.

Treatment of severe autoimmune disorders with autologous and allogeneic hematopoietic cell transplantation is an emerging and potentially efficacious clinical strategy. Snowden and colleagues evaluate a 20-year analysis of the European Society for Blood and Marrow Transplantation registry, demonstrating important and interesting trends.

The local microenvironment plays a critical role in the formation of the hemostatic plug during hemostasis. Shen and colleagues studied the coordinated contribution of different hemostatic factors in detail using a combination of genetic and pharmacological approaches.


Familial hemophagocytic lymphohistiocytosis (HLH) type 3 is due to mutations in the UNC13D gene, which encodes the Munc13-4 protein. To date, the only curative therapy is allogeneic hematopoietic cell transplantation. In the study by Soheili and colleagues, UNC13D gene transfer into hematopoietic stem cells corrected all clinical and biological signs of disease in a murine model of HLH. This study demonstrates alternative pathways for the treatment of this disease.

It has been reported that individuals with monoclonal gammopathy of undetermined significance (MGUS) have an increased risk of bony fractures. To explore this in greater detail, Thorsteinsdottir and colleagues analyzed the AGES-Reykjavik Study cohort comparing the 300 individuals with MGUS amongst the cohort of over 5000 other individuals and made important findings.


Featured Visual Abstract

Gene transfer into hematopoietic stem cells reduces HLH manifestations in a murine model of Munc13-4 deficiency

Key Points
- UNC13D gene transfer into HSCs corrects all clinical and biological signs of HLH in a mouse model.
- Munc13-4 is expressed in mature CD8+ T cells allowing the correction of cytotoxic activity and consequently efficient viral restriction.




Blood Advances is the open-access journal of the American Society of Hematology (ASH) (, the world’s largest professional society concerned with the causes and treatment of blood disorders.

ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.