Issue Archive

In a Perspective, Fennell et al review the current state of epigenetic therapies for acute myeloid leukemia, highlighting their proposed mechanisms of action, the role of the immune system in mediating their response, and the outlook for new agents and combined therapies to maximize their potential efficacy.

Stein and Martin provide a review of the thrombotic and bleeding complications of myeloproliferative neoplasms and provide a roadmap for appropriate therapy.

In a retrospective analysis, Dickerson et al report that the incidence of hypertension in patients treated with ibruitinib is nearly 80% and is associated with an increased rate of adverse cardiovascular events, primarily atrial fibrillation. Cardiac events can be reduced by treating the hypertension.

Thompson and colleagues report that detection of minimal residual disease using next-generation sequencing, which is 2 orders of magnitude more sensitive than flow cytometry, is a much better predictor of progression-free survival.

Park et al describe a novel KLF4-mediated pathway that promotes chromic myeloid leukemia (CML) stem cell (LSC) survival. Deletion of KLF4 in a mouse model of CML decreases LSC survival through repression of Dyrk2, resulting in c-Myc depletion and increased p53 activity.

Tissue factor pathway inhibitor (TFPI) inhibits coagulation initiation, and TFPI inhibition enhances the activation of factor X by tissue factor. Shapiro et al report the results of a phase 2 study of prophylactic administration of the TFPI inhibitor concizumab for bleeding prevention in hemophilia, reporting efficacy in Factor VIII and IX deficiency even in patients with inhibitors to Factor VIII or IX.

Intrauterine transplantation induces tolerance in the setting of the immature immue system but is hampered by low levels of engraftment. Glycogen synthase kinase 3 (GSK3) inhibition enhances stem cell proliferation, and Loukogeorgakis and colleagues report excellent engraftment in utero in mice following surface attachment of nanoparticles loaded with GSK3 inhibitor to donor stem cells.