(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.
Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation, Hottz et al.
Dengue is the most frequent hemorrhagic viral disease and re-emergent infection in the world. While thrombocytopenia is characteristically observed in mild and severe forms of dengue, the role of platelet activation in the pathogenesis of this disease has not been elucidated. This week in Blood, investigators report increased expression of IL-1β in platelets and platelet-derived microparticles from patients with dengue or after platelet exposure to dengue virus in vitro, demonstrating that dengue virus infection leads to assembly of NLPR3 inflammasomes, which activates caspase-1 and caspase-1-dependent IL-1β secretion. In a series of elegant experiments, investigators present comprehensive evidence that platelets contribute to increased vascular permeability in dengue virus infection by inflammasome-dependent release of IL-1β. These novel data on platelet biology provide critical insight into the mechanisms of the increased vascular permeability characteristic of dengue fever.
Comprehensive analysis of PTEN status in Sezary syndrome, Cristofoletti et al.
Sezary syndrome is an incurable leukemic variant of cutaneous T-cell lymphoma characterized by recurrent chromosomal alterations, among which chromosome 10q deletion is frequent. In this week’s issue of Blood, investigators publish findings from a study of the phosphatase and tensin homolog (PTEN) status on locus 10q23 in 44 patients with Sezary syndrome, reporting that PTEN was deleted in 36 percent of the patients whereas a PTEN downregulation on the mRNA and protein level was observed in almost all patients. While it appears that somatic mutations, promoter hypermethylation, and PTENP1 deletions are not involved in the suppression of PTEN function, in the manuscript investigators demonstrate that PTEN level can also be suppressed by a group of miRs (microRNAs) previously found to be upregulated and of prognostic relevance in Sezary syndrome. As this is the first study to fully explore the PTEN status in a large cohort of patients with Sezary syndrome, these findings unveil potential elements of clinical utility in this malignancy.
Exposure to ultraviolet radiation and risk of Hodgkin lymphoma: a pooled analysis, Monnereau et al.
While ultraviolet (UV) radiation exposure has been inversely associated with Hodgkin lymphoma risk, reporting has been inconsistent, sparse, and without attention to Hodgkin lymphoma heterogeneity. The authors of this study conducted a pooled analysis of Hodgkin lymphoma risk focusing on type and timing of UV radiation exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1,320 Hodgkin lymphoma cases and 6,381 controls. After estimating lifetime, adulthood, and childhood UV radiation exposure and history of sunburn and sunlamp use in the study subjects, investigators observed statistically significant inverse associations between childhood and adulthood UV radiation exposures, sunburn history, and sunlamp use with Hodgkin lymphoma risk but did not find significant dose-response relationships. As risks are demonstrated to be significant only for EBV-positive Hodgkin lymphoma, investigators report that increased UV radiation exposure may protect against Hodgkin lymphoma and particularly against EBV-positive Hodgkin lymphoma. Plausible mechanisms involving UV radiation induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new disease prevention targets.
Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia, Willems et al.
Cancer cells require nutrients and energy to adapt to increased biosynthetic activity. For example, glutamine contributes to leucine import into cells, which controls the amino acid/Rag/mTORC1 signaling pathway. This week in Blood, investigators demonstrate that glutamine removal inhibits mTORC1 and induces apoptosis in acute myeloid leukemia (AML) cells. Furthermore, investigators report the knockdown of the SLC1A5 high-affinity transporter for glutamine induces apoptosis and inhibits tumor formation in a mouse AML xenotransplantation model. In additional studies, both in cell lines and in a large collection of primary AML samples, authors present data indicating that compounds like L-asparaginase and other L-ases are effective in inhibiting this signaling cascade by reducing glutamine levels. Glutamine uptake inhibition reduces mTOR activity, activates strong protective autophagy, and increases apoptosis in AML, therefore presenting a promising anti-leukemic strategy.
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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