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 email@example.com.
CD39 Target Practice
Delayed targeting of CD39 to activated platelet GPIIb/IIIa via a single-chain antibody: breaking the link between antithrombotic potency and bleeding?, Hohmann et al.
The NTPDase CD39, which degrades main platelet activating/recruiting agent ADP, represents a promising antithrombotic therapeutic. In this week’s Plenary Paper Hohmann and colleagues examine the targeting of CD39 to a developing clot via a single-chain antibody specific for glycoprotein IIb/IIIa and thus for platelets only once activated. In their manuscript Hohmann and colleagues report that the specific binding of this construct (targ-CD39) to activated platelets which caused its antithrombotic potency to increase significantly. The targ-CD39 construct exhibits great potential as a novel antithrombotic treatment, as it breaks the link between effective blood clot prevention and bleeding complications.
Epigenetics in hematology: introducing a collection of reviews
The role of chromatin modifiers in normal and malignant hematopoiesis, Butler and Dent.
This week’s issue of Blood marks the launch of a new review series exploring exciting new findings linking epigenetic dysregulation to the pathogenesis of a number of hematologic diseases. This first review of the series discusses the fundamentals of epigenetic mechanisms and their role as regulators in hematopoiesis. The review provides a framework for understanding the role of these regulators in the clinical arena to be covered in future reviews and explores the specific associations of many epigenetic mechanisms with lymphoid malignancies, myeloid malignancies, myelodysplastic syndrome, and MLL oncogene-associated disease. The overall objective of this focused review series is to provide a comprehensive update of this field and develop research and clinical goals for the next decade
Loss-of-function of the protein kinase C delta (PKC ) causes a B cell lymphoproliferative syndrome in humans, Kuehn et al.
B cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta, Salzer et al.
Primary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies that are often associated with autoimmunity leading to significant morbidity; however, the underlying genetic etiology in the majority of patients has remained elusive. In this week’s issue of Blood, Kuehn and colleagues describe a single patient with a relatively common phenotype but a new gene defect. The disease phenotype is characterized by polyclonal B cell activation with lymphoproliferation, low grade EBV (Epstein Barr virus), viremia, and unexplained natural killer (NK) cell dysfunction. In a parallel paper in the same issue of the journal, Salzer and colleagues report the identification of the same novel monogenetic gene defect in a patient from a consanguineous family suffering from recurrent infections and severe lupus-like autoimmunity.
The two studies describe a disorder characterized by similar symptoms including lymphadenopathy and positive autoantibodies, phenomena caused by B-cell hyperproliferation and NK dysfunction, associated with chronic low grade EBV infection. Both studies identify a similar homozygous, loss-of-function mutation in protein kinase C delta (PKCD) that disrupts control of B-cell proliferation and apoptosis and affects NK cell cytolytic activity as the cause of the disease. Thus these two papers in tandem describe the first two cases of a novel disease based on PRKDC deficiency.
Reporters who wish to receive a copy of any of the manuscripts highlighted above or would like to request an interview with the authors may contact Andrea Slesinski at 202-552-4927 or firstname.lastname@example.org
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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