(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email firstname.lastname@example.org.
Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis, Lechtenberg et al.
A seminal study published this week in Blood reports the first determination of the crystal structure of the prothrombinase complex, providing illuminating insights into one of the most important structures in coagulation. In the manuscript Lechtenberg and colleagues present the crystal structure of a system that is homologous to the prothrombinase complex, composed of the protease factor (f)Xa and cofactor fVa, that efficiently converts prothrombin into thrombin by specific, sequential cleavage at two sites. Insufficient thrombin generation is the root cause of hemophilia and excessive thrombin production results in thrombosis. Thus, with this discovery, we can now understand how factor Va, Xa, and thrombin assemble to produce active thrombin. The elucidation of this long-sought-after structure has not only considerable scientific relevance but will also likely drive future drug development.
Defining characteristics of classical Hodgkin lymphoma microenvironment T helper cells, Greaves et al.
While CD4+ T-helper cells (TH) dominate the classical Hodgkin lymphoma (CHL) microenvironment, their role in this disease has yet to be completely understood. A study published this week in Blood demonstrates the existence of a predominant TH1 phenotype of the infiltrating CD4+ T cells in the Hodgkin lymphoma microenvironment and that CD4+ T cells are not anergic, advancing our general understanding of the T cells involved in Hodgkin lymphoma and their potential pathophysiological role. This finding provides new insight into how these T cells can interact with the Reed-Sternberg cells by CD30L expression and how they might contribute to shaping the microenvironment in Hodgkin lymphoma by attracting inflammatory cells. These molecular insights into the classical Hodgkin lymphoma-associated T-helper cells offer potential diagnostic, prognostic, and pharmacologically modifiable therapeutic targets.
NETosis: how vital is it? Yipp and Kubes.
In a topical review in this week’s issue of Blood, authors examine the critical role of neutrophil extracellular traps (NETs) in innate immunity, discussing how NETs are formed in response to various stimuli and providing evidence that NETosis is not universally a cell death pathway. In the review Yipp and Kubes describe at least two different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. They also evaluate the evidence for NETs in catching and killing pathogens. Finally, Yipp and Kubes discuss how infections are related to the development of autoimmune and vasculitis diseases through unintended but detrimental bystander damage resulting from NET release.
A role for IRF4 in the development of CLL, Zhong and Byrd.
Interferon regulatory factor 4 (IRF4) is a critical transcriptional regulator of B-cell development and function. In this week’s issue of Blood, Zhong and Byrd detail results of their utilization of a genome-wide single-nucleotide polymorphism (SNP) association study of a novel CLL mouse model to identify IRF4 as a major susceptibility gene in chronic lymphocytic leukemia (CLL). Investigators generated the model by cross-breeding mice carrying Vh11 gene knock-in with mice displaying knock-out of IRF-4 gene. The study is the first to demonstrate a causal relationship between low levels of IRF4 and the development of CLL. The IRF4-/-Vh11 mouse model of CLL is not only valuable for dissecting the molecular pathogenesis of CLL, but may also be used for therapeutic purposes.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), 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.
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