2013-02-28

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 aslesinski@hematology.org.

Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation, Haroche et al. 

The discovery that mutations in the BRAF gene, an oncogene, lead to alterations in the cellular signaling machinery of various cancers has led to the development of BRAF inhibitor therapies. For the first time, in this manuscript authors report the dramatic clinical activity of the BRAF inhibitor vemurafenib in two patients with progressive Erdheim-Chester Disease (ECD) and so-called Langerhans histiocytosis with a BRAFV600E mutation. ECD is a rare systemic disease characterized by the infiltration of tissues and organs by histiocytic cells leading to diverse and sometimes fatal manifestations. Investigators report a dramatic clinical response in both patients as early as 30 days from the initiation of vemurafenib treatment, providing important therapeutic promise for the approximately half of ECD patients who carry the BRAF mutation. These observations suggest that vemurafenib could become a valuable novel therapy for patients with this potentially fatal condition for which only several active therapeutic options are available.

Mortality increases after massive exchange transfusion with older stored blood in canines with experimental pneumonia, Solomon, et al.

While there is unanimous agreement among clinicians that massive blood transfusions are a valuable treatment for newborn infants with severe infection, the question as to whether fresh or readily available long-stored red blood cells are superior for transfusion has not been answered. In this manuscript, authors detail the results of a series of experiments on the effect of red cell storage duration on the mortality of dogs with bacterial pneumonia undergoing massive transfusion. They demonstrate that dogs transfused with large volumes of long-stored red blood cells (40-42 days) had clinically significant negative effects as compared to dogs transfused with fresh blood. These striking results provide novel insights into mechanisms determining poor outcomes after transfusion of comparatively old red blood cell products.

Gli3-mediated hedgehog inhibition in human pluripotent stem cells initiates and augments developmental programming of adult hematopoiesis, McIntyre, et al.

Improving the hematopoietic differentiation process of pluripotent stem cells holds great promise for their therapeutic application for a range of blood diseases. In this manuscript, authors report results of experiments using chemical activators and inhibitors and suppressed or over-expressed regulators to manipulate a critical pluripotent stem cell differentiation pathway known as the hedgehog pathway. Experimental data show that augmentation of the hedgehog intracellular pathway alters the output from human pluripotent stem cells to provide hematopoietic cells that have acquired some aspects of adult hematopoiesis. These findings signal a great advance for the fields of developmental biology and regenerative medicine.

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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