Volume 1, Issue 3


Cover Figure: Immunohistochemical image of S100A9-expressing neutrophils that accumulate at the core of guinea pig lung granulomas.
See the article by Yoshioka et al.

Join the discussion of this issue's Point-Counterpoint articles in Blood Advances Community Conversations

WASHINGTON, December 27,  2016 – 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.

There has been much interest in the impact of immune function on disease burden and mechanisms of tumor cell escape. The paper by Quek et al explores the mutational landscape of acute myeloid leukemia cells following relapse after allogeneic bone marrow transplantation. Of particular note is their analysis of 29 patients whose samples were compared before and after transplantation; 13 patients showed a significant change in the mutational profile. This study convincingly demonstrates the mechanisms of tumor cell escape and the need to identify novel strategies to address the problem of relapse following transplantation.

The formation of granulomas is a mysterious process in a number of diseases. The paper by Yoshioka et al explores the role of neutrophils and in particular a calcium-binding protein of the S100 family that can be targeted with a monoclonal antibody or a specific inhibitor that impaired the formation of granulomas. This study sheds new light on granuloma formation, the role of neutrophils in the process, and approaches that may be used clinically to impair granuloma structure.

Natural killer (NK) cells have been implicated in a variety of important functions, including protection from infectious insults, especially from viruses, and immune surveillance of malignancies. In the posttransplant setting, NK cells are often the first immune cells that recover. The study by Bergerson et al found that more robust recovery of NK cells in the first month after double umbilical cord blood transplantation was associated with improved disease-free survival. Furthermore, the NK cell–active cytokine interleukin-15 may result in improved NK cell numbers and function, suggesting a role for this cytokine in the posttransplant setting.

In a commentary, Patel et al explore the genetic analysis of B-cell lymphomas associated with hemophagocytic lymphohistiocytosis, which is often an aggressive, life-threatening illness and is thought to be characterized by excessive immune activation. Utilizing a National Cancer Institute database, the authors identified 16 cases, many of which had abnormalities suggesting alterations in genes associated with immune evasion. Their analysis suggested that evaluation of immune modulatory agents (for example, directed against PD-1) may be rational targets for future therapeutic intervention.

There is extraordinary excitement in the potential for immune-based therapies for treating a broad range of cancers, including hematological malignancies. The development of cellular immunotherapies, for example, with the use of chimeric antibody receptors (CARs) and bispecific antibody constructs, holds great promise for the treatment of acute lymphoblastic leukemia. In our Point-Counterpoint discussion for this issue, Davis and Mackall highlight CAR T-cell–based approaches, whereas Jabbour and Kantarjian focus on antibody concepts. We hope you enjoy these discussions, and we welcome your comments and views.

Dutta et al report on a simple, inexpensive assay to diagnose mutations in patients with hemophilia A and carriers of this abnormality. This approach may aid in the more accurate diagnosis of the disorder in these individuals.

Featured Visual Abstract

Neutrophils and the S100A9 protein critically regulate granuloma formation

Yuya Yoshioka, Tatsuaki Mizutani, Satoshi Mizuta, Ayumi Miyamoto, Satoru Murata, Toshiaki Ano, Hiroshi Ichise, Daisuke Morita, Hiroyuki Yamada, Yoshihiko Hoshino, Tatsuaki Tsuruyama, Masahiko Sugita





Blood Advances is the official 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.