The week in blood

Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of blood.

An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults

Previously defined response criteria for myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) are inadequate to estimate response, in particular in the “overlap” syndromes that share dysplastic and proliferative pathological features of hematopoiesis. In this week’s issue of Blood, an international consortium of clinical investigators proposes uniform response criteria for MPN/MDS overlap disorders in adults. Their effort to harmonize histopathologic (marrow) and laboratory responses as well as certain clinical parameters and symptom scores furnishes a valuable contribution to speaking a common language in the field.

DNA methylation profiling identifies 2 splenic marginal zone lymphoma subgroups with different clinical and genetic features

Epigenetic mechanisms, including DNA methylation, play an important role not only in the development and maturation of normal cells, but also in the development and progression of neoplastic cells. In their study in Blood, Arribas et al show that DNA methylation profiling identifies two markedly distinct subtypes of splenic marginal zone lymphoma with both different clinical and genetic features. These findings provide an opportunity to better understand the biology of marginal zone lymphoma and develop therapy to reverse the high methylation phenotype, and thus target malignant B cells.

Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma

Limited-stage mycosis fungoides (MF) refractory to skin-directed therapies and advanced stage MF and Sezary syndrome (SS) are incurable with currently available therapies, with the exception of allogeneic stem cell transplantation. In this issue of Blood, Duvic et al demonstrate that mogamulizumab, a humanized monoclonal antibody targeting the chemokine receptor CCR4, is well tolerated and has significant clinical activity (objective responses 36.8%, median duration 10.4 months) in heavily pretreated patients with MF and SS.

Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar

Proteases initiate signaling pathways in a variety of cell types via the protease-activated receptors (PARs), which are a family of G-protein coupled receptors that can initiate signaling through multiple G-protein pathways. PAR1 was originally identified as the receptor responsible for thrombin-induced activation of platelets. In this issue of Blood, Aisiku et al. describe a novel class of PAR1 inhibitors that block proinflammatory pathways, but spare cytoprotective signaling in endothelial cells. These compounds, parmodulins, may have therapeutic advantages compared to the currently known inhibitors, including their ability of preserving the APC-mediated vascular protective effect of PAR1. These agents might, for instance, be safer with respect to bleeding complications.

Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment for refractory adenovirus infection after HSCT

Adenovirus infection remains a major problem, particularly in pediatric allogeneic stem cell transplant recipients. In their manuscript in this week’s Blood, Feucht and colleagues investigate the safety and clinical activity of the adoptive transfer of interferon gamma captured Adv-specific T cells administered to 30 allogeneic transplant recipients with refractory adenovirus infection. They demonstrate that the infusions of the adenovirus specific T cells are safe and the adoptive transfer of small cell doses is associated with clinical benefit in the majority of cases.

The role of the ADAMTS13 cysteine-rich domain in VWF binding and proteolysis

In the past decade, significant progress has been made as regards our understanding of the structural and functional relationships of ADAMTS13 and von Willebrand factor. The data available to date suggest that the recognition and productive cleavage of VWF depend on the amino-terminal portion of ADAMTS13. The role of more distal domains of ADAMTS13 is incompletely understood. In this issue of Blood, de Groot et al elegantly further elucidate the structure-function role of ADAMTS13 in proteolysis of VWF and demonstrate a hydrophobic pocket in the Cys-rich domain of ADAMTS13 that appears to directly interact with a hydrophobic pocket in the VWF-A2 domain.

How I treat incidental pulmonary embolism

Incidental pulmonary embolism is a frequent diagnosis, particularly in cancer patients, and poses a challenge in clinical practice. Using three clinical case scenarios, O’Connell reviews the approach to evaluating and managing such patients.

Contribution by Uziel Perez club memberships white coat