(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 email@example.com.
Reperfusion of cerebral artery thrombosis by the GPIb/vWF blockade with the nanobody ALX-0081 reduces brain infarct size in guinea pigs, Momi et al.
The only approved therapy for stroke, the second leading cause of death and disability throughout the world, is intravenous tissue plasminogen activator (tPA) applied within a narrow timeframe after onset. Although tPA can often recanalize vessels, reperfusion injury limits the therapeutic impact of this intervention and disability frequently remains extensive. In this week’s issue of Blood, Momi and colleagues demonstrate in a guinea pig model that inhibition of vWFGP1b-platelet interactions dissolves vascular occlusions and reduces infarct size without an increase in intracerebral hemorrhage. These exciting results demonstrate the key role of platelets in cerebrovascular events and highlight the important distinction between inhibition of GP1b, which appears not to increase the risk of intracranial hemorrhage, and GPIIb/IIIa, which does.
The Thr224Asn mutation in the VPS45 gene is associated with congenital neutropenia and primary myelofibrosis of infancy, Stepensky et al.
Approximately 60 percent of severe congenital neutropenia (SCN) is attributable to mutations in neutrophil elastase, while another 10-20 percent of cases arise from mutations in HAX1, G6PC3, GFI1, G6PT1, WAS, and CSF3R. The genetic basis for the remaining 20-30 percent of cases is unknown. In this week’s issue of Blood, Stepensky and colleagues describe homozygous mutations of VPS45 in five patients who had SCN and infantile myelofibrosis from consanguinous families, observing that VPS45 encodes for a protein that contributes to the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex which is important in trafficking protein to intracellular organelles. This study not only establishes a new gene in the spectrum of SCN, but also reports that the role of VPS45 in trafficking links this syndrome to a set of syndromes of defective protein trafficking, including Chediak-Highashi syndrome, Hermansky-Pudlak syndrome, and Griscelli syndrome, all of which are associated with immunodeficiency and neutropenia.
Therapy prolongation improves outcome in multi-system Langerhans cell histiocytosis, Gadner et al.
In this week’s issue of Blood, Gadner and colleagues provide data from the third in a series of studies supported by the Histiocyte Society aimed at improving outcomes for patients with multi-system Langerhans cell histiocytosis (MS LCH). In this study, investigators examined a) the impact of adding methotrexate (MTX) to the standard therapy regimen for MS LCH patients with high-risk organ involvement and b) the effect of increasing maintenance therapy from six to 12 months in patients without risk of organ involvement. Investigators observed that adding MTX did not improve outcomes in patients with high-risk organ involvement; however, they observed a significant decrease in disease reactivation among patients with lower-risk disease who received prolonged maintenance therapy. Surprisingly, despite the failure of MTX to improve outcomes in higher-risk patients, the overall survival of all patients was superior to that reported in previous studies using the same chemotherapy. This time-dependent improvement remains unexplained. However, the poor outcome of nearly two-thirds of MS LCH patients who do not respond well to initial therapy underscores the need for further studies to explore targeted therapies or alternative approaches to improve response rates and long-term survival in patients with this rare disorders.
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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