(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.
Loss of the F-BAR protein CIP4 reduces platelet production by impairing membrane-cytoskeleton remodeling, Chen et al.
Megakaryocytes generate platelets via long proplatelet processes, which function as intermediate structures in platelet production. This process involves extensive reorganization of the cytoskeleton and plasma membrane, and, for more than 50 years, insights into the mechanistic and molecular structure and function of this membrane system during platelet formation have been scant. In this week’s Plenary Paper, investigators utilize knockout mice and various other methods to demonstrate that impaired platelet production and thrombocytopenia occur from loss of Cdc42 (CIP4), a so-called F-BAR protein that localizes to membrane phospholipids. While investigators did not observe a change in the number of megakaryocytes and their progenitors in this process, the appearance of proplatelet protrusions and platelet release was impaired, as loss of CIP4 resulted in a more rigid membrane. These findings revealing a novel, crucial role for CIP4 and supporting a new biophysical mechanism for platelet biogenesis represent a major advance in the field of platelet/megakaryocyte biology.
A novel role for C3 in antibody-induced red blood cell clearance and antigen modulation, Girard-Pierce et al.
While hemolytic transfusion reactions (HTRs) that arise as a result of incompatible red blood cell (RBC) transfusions are a leading cause of transfusion-associated deaths, the topic remains poorly understood in the transfusion community. Although many transfused incompatible RBCs are cleared, some remain in circulation despite the presence of RBC-specific antibodies. In this week’s issue of Blood, investigators report the results of experiments in which they generated a unique murine model with RBC-specific expression of a clinically relevant human antigen (KEL2) to better understand incompatible RBC clearance. They observed that RBC with similar levels of antigen appear to survive normally following an initial wave of hemolysis caused by a specific antibody. The authors propose a mechanism involving membrane modification that could explain why incompatible blood transfusion does not always result in complete elimination of transfused cells. This HTR model may also serve as a platform to test strategies to inhibit incompatible RBC clearance, thus potentially mitigating transfusion dangers.
Differences in gene expression and cytokine levels between newly diagnosed and chronic pediatric ITP, Jernås et al.
Immune thrombocytopenia (ITP) is a relatively common hematologic autoimmune bleeding disorder in which platelets are prematurely destroyed. While the disease is self-limited and resolves within 12 months in the majority of children with ITP, it becomes chronic in approximately 20 percent of all pediatric cases. As no predictive test currently exists to identify a child’s susceptibility for chronic ITP, the development of such would enable critical early therapeutic intervention to take place that would likely improve recovery. In this week’s issue of Blood, investigators report the results of a DNA microarray analysis of T cells from children with both newly diagnosed and chronic ITP. They observed complete separation of the gene expression profiles between the two forms of the disease and also note that the gene expression levels of several cytokines differed between the newly diagnosed and chronic phases of the disease. Investigators also observed that plasma from children with newly diagnosed ITP contained higher levels of IL-16 and lower levels of IL-4 than that of children with chronic ITP. These data indicate that chronic ITP in childhood is a distinct disease entity that is biologically dissimilar with respect to T-cell gene expression and cytokine levels.
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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