Issue Archive

The process of angiogenesis contributes to leukemogenesis, indicating a place for angiotargeting therapy in the treatment of AML. In this issue of Blood, Madlambayan and colleagues demonstrate that combining antivascular agents that target endothelial cells and modulate the local cytokine network can be an effective therapeutic strategy in the fight against leukemia.¹  The authors combined the VEGF-specific antibody bevacizumab with the vascular disrupting agent OXi4503. This combination may soon become a clinical reality: bevacizumab is already in clinical use and a clinical trial of OXi4503 in treatment of AML was recently registered (ClinicalTrials.gov identifier: NCT01085656).

In this issue of Blood, Waage and colleagues present a phase 3 study comparing the combination melphalan-prednisone-thalidomide (MPT) with melphalan-prednisone plus placebo (MP) for the treatment of elderly patients with multiple myeloma. Though responses were in favor of MPT, they did not translate in prolonged progression-free or overall survival.

In this issue of Blood, Li et al report that JAK2-V617F increases DNA damage and impairs hematopoietic stem cell function in a conditional knock-in mouse model of JAK2-V617F–positive essential thrombocythemia.¹ 

In this issue of Blood, Meissner and colleagues discover that immune cells from CGD patients that have defective phagocyte oxidases show hyperactive inflammasome activation. These findings implicate that ROS down-regulate rather than enable caspase-1 activation and identify anti–IL-1 strategies as a potential therapy for the disproportionate inflammatory responses associated with CGD.

In this issue of Blood, Connolly and colleagues describe an elegant approach to studying the significance of specific molecular interactions in vivo. The authors have “knocked-in” a mutant form of the protease, urokinase-type plasminogen activator (uPA), into the murine uPA locus, to create a mouse strain (Plau^GFDhu/GFDhu) where the interaction between endogenous uPA and its receptor (uPAR) is selectively disrupted, while leaving other functions of both uPA and uPAR intact. Their findings suggest that the primary role of uPAR in vivo is to promote fibrinolysis within tissues through localization of uPA, and that many of the previously described activities of uPAR may be secondary to this process.¹