Issue Archive

Many new drugs for the treatment of acute myeloid leukemia have emerged over the past 2 years. DiNardo and Wei use 3 cases to illustrate how availability of these new agents is driving a reappraisal of the treatment decision-making process and providing a practical guide for choosing appropriate tailored therapies.

Steroids are conventional frontline therapy for acute graft-versus-host disease (GVHD) but induce substantial toxicity. This randomized multicenter comparison of sirolimus vs prednisone for treatment of standard-risk acute GVHD demonstrates similar response rates at 28 days. Sirolimus therapy was associated with reduced steroid use and improved quality of life.

The authors investigate the effect of combined activated NF-κB and Notch signaling, a combination that has been observed in subsets of B-cell lymphoma. They demonstrate in a mouse model that the combined activation induces lymphoma and further links the combination to secondary myeloid leukemia, a rare but observed phenomenon arising in patients with lymphoma.

Activated B-cell–like diffuse large B-cell lymphoma (ABC-DLBCL) is more aggressive than its germinal center B-cell–like counterpart. Bucher et al demonstrate that DLBCL displays calcineurin-dependent constitutive NFAT activation and, in preclinical models, calcineurin inhibitors are uniquely toxic to ABC-DLBCL.

About 25% of myeloproliferative neoplasms are caused by mutant calreticulin (CALR), which has been demonstrated to stimulate megakaryocyte proliferation by ligand-independent binding to the thrombopoietin receptor. Di Buduo and colleagues report that mutant CALR also shows loss of binding to calcium-regulatory proteins, leading to constitutive increase in intracellular calcium, further increasing proliferation of megakaryocytes, and contributing to their prominence as a clinical feature.

Factor XIII (FXIII) stabilizes the fibrin clot and circulates as a tetramer. The authors identify the critical residues for interaction of FXIII subunits, mutations in which have been reported to be associated with congenital FXIII deficiency.