Volume 2, Issue 15


Cover Image

Cover Figure:Plots illustrating changes in chromatin during differentiation from hematopoietic stem and progenitor cells (HSPCs) to erythroblasts. Promoters silenced in erythroblasts and promoters silent in both HSPCs and erythroblasts exhibit much more dramatic chromatin changes than promoters activated in erythroblasts. See the article by Bartholdy et al.

WASHINGTON, August 14,  2018 – 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.

Chronic graft-versus-host disease can be one of the most debilitating treatment-related challenges after allogeneic transplantation. Recently, the B-cell receptor signaling inhibitor ibrutinib has been explored in this area, resulting in the first US Food and Drug Administration–approved treatment for this disease. Jaglowski and Blazar discuss the rationale, preclinical data, and clinical effects of this promising treatment.

It is well recognized that aplastic anemia can be cured with allogeneic transplantation, especially in young patients with HLA-matched sibling donors. However, in recent years exciting progress has been achieved with older patients and those with matched unrelated donors and haploidentical donors. These trends are discussed in a review by Georges, Doney, and Storb, who have led many studies in this area.

DNA double-strand breaks occur as part of normal physiology, and there are several disease states whose cause is inadequate or defective DNA repair. One such disease is DNA ligase 4 deficiency (LIG4-SCID). Accurate diagnosis is difficult and time consuming. Buchbinder and colleagues developed a radiosensitivity flow-based assay to rapidly diagnose LIG4-SCID. It is likely to be able to diagnose other conditions also.

Waldenström macroglobulinemia (WM) is an indolent B-cell malignancy impacted by cytokines that include interleukin 6 (IL-6) and IL-21. Little is known about the role of checkpoint inhibitors in this disease. Jalali et al investigated the impact of these cytokines on programmed death ligand 1 (PD-L1) and PD-L2 expression in WM cell lines and patient samples, highlighting the potential role of checkpoint inhibitors in the treatment of this disease.


Ibrutinib is a highly active oral drug that has significant efficacy in chronic lymphocytic leukemia as well as other B-cell malignancies. However, given the cost of this drug, a question is whether it is cost-effective, especially in patients without a 17p deletion. Barnes and colleagues address this question.

In sickle cell disease, excessive plasma adenosine has been found to impact pathogenesis. Liu et al explored CD73-mediated erythrocyte adenosine signaling in the pathogenesis of red blood cell sickling, demonstrating a potential novel therapeutic target.

Strategies to reduce platelet aggregation and arterial thrombosis are needed in a variety of disease settings. Nayak and colleagues take an interesting approach, altering glucose uptake and aerobic glycolysis in activated platelets using an inhibitor of pyruvate dehydrogenase. Biochemical end points were reached, which may set the stage for clinical evaluation of this strategy.

Graft-versus-host disease (GVHD) is one of the major challenges for patients undergoing allogeneic transplantation, and the accurate assessment of risk is an area of much interest. Holtan and colleagues explored the impact of amphiregulin, an epidermal growth factor receptor ligand that helped define risk of patients who developed acute GVHD.



Featured Visual Abstract

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial)

Strategies to reduce vaso-occlusive episodes in patients with sickle cell disease (SCD) is an important clinical goal. Daak and colleagues explore a novel approach of altering docosahexanoic acid, which is known to be low in blood cell membranes of patients with SCD. They report important clinical end points in this phase 2 double-blind randomized trial that support further investigation of this agent.





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.