(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.
MEK inhibitors selectively suppress alloreactivity and graft-versus-host disease in a memory stage-dependent manner, Shindo et al.
T-cell depletion has been used in stem cell transplant to prevent graft-versus-host disease (GVHD); however, since this practice slows immune reconstitution, it unfortunately predisposes patients to infection. In this week’s Plenary Paper, Shindo and colleagues further explore the observation that different subsets of T cells mediate alloreactivity and virus-specific T-cell reactivity, respectively. Alloreactive T cells are largely contained within the pool of naive and central memory T cells, while a more differentiated memory T cell population allows for antiviral protection. In this manuscript, Shindo and colleagues demonstrate that naive T cells prefer to activate the RAS/MEK/ERK pathway and that MEK inhibition reduces development of alloreactivity without affecting cytomegalovirus and Epstein-Barr virus-specific viral responses. This finding could have great potential for selective functional T-cell depletion to prevent GVHD without reducing antiviral responses.
Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia, Boyle et al.
Splenectomy is a leading second-line therapy for the treatment of idiopathic thrombocytopenic purpura (ITP) and for many leads to permanent control of the disease. Unfortunately, it can be associated with a risk of intra-abdominal clot formation and a long-term risk of severe sepsis, yet the magnitude of risk of splenectomy-related complications remains poorly defined. In this week’s issue of Blood, Boyle and colleagues examine risk for developing such complications in a large cohort of 10,000 ITP patients, of whom more than 1,700 had undergone splenectomy. Following their investigation, authors confirm an increase in early abdominal venous thromboemolism (deep vein thrombosis and pulmonary embolism; VTE) following splenectomy, yet also concluded that these patients had an increased long-term risk of developing VTE as well as a slightly increased risk of sepsis; however, the risk ultimately remained quite low. Interestingly, investigators conclude that splenectomized patients had a lower mortality when compared to ITP patients without splenectomy. Whether these findings reflect a protective effect of splenectomy or differences in patient selection for splenectomy remains to be determined.
MicroRNAs activate natural killer cells through toll-like receptor signaling, He et al.
MicroRNAs (miRNAs) bind complementary sequences in target RNAs, targeting them for degradation or silencing them through inhibition of translation. Most studies of miRNA focus on their impact on intracellular events and many have demonstrated that miRNAs circulate in the blood, yet the question of whether they are a byproduct of cell turnover or have a unique cellular function is actively debated. In this week’s issue of Blood, He and colleagues demonstrate the ability of extracellular miRNAs to activate natural killer (NK) cells. Their manuscript suggests that miRNAs signal through the toll-like receptor 1 (TLR1) to activate NFκB, leading to NK activation and also to potent anti-tumor effects in vivo. These observations have significant clinical implications, suggesting that miRNA might be used to modulate NK cell responses to infection or to tumor cells.
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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