Issue Archive

The exchange of mitochondria between intimately connected cells of different types that function collaboratively is an area of intense scientific interest. Golan and colleagues used elegant murine models to show how transfer of mitochondria from transplanted hematopoietic stem and progenitor cells (HSPCs) to bone marrow mesenchymal stem cells (MSCs) occurs. Healthy donor HSPCs not only reconstitute the hematopoietic system after transplantation but also support and induce the metabolic recovery of their irradiated, damaged MSCs via mitochondria transfer.

New drugs are emerging as treatment options for patients with light-chain (AL) amyloidosis. In this timely review, Palladini et al first remind us of the importance of ensuring a precise diagnosis and then discuss a framework for care of newly diagnosed patients and those with relapsed or refractory disease.

Zinzani et al report the results of the open-label, randomized phase 2 CONTRALTO study, which evaluated addition of the BCL-2 inhibitor venetoclax to bendamustine plus rituximab in patients with relapsed/refractory follicular lymphoma. Despite the prominence of BCL-2 in the pathophysiology of follicular lymphoma, no meaningful efficacy benefit was observed and toxicity was increased. This negative trial has implications for how BCL-2 inhibitors are investigated in treatment regimens for follicular lymphoma.

Ghosh et al report the clinical spectrum of rare patients with deficiencies of either CD27 or CD70, the components of a receptor-ligand pair pivotal to the immunological control of Epstein-Barr virus. As well as virus-mediated immune dysregulation and autoinflammation, there is a marked predisposition to lymphoma. Patients can have excellent outcomes with allogeneic transplants.

Bone disease in multiple myeloma is a serious clinical problem. Westhrin and colleagues present novel data that demonstrate a causative role for monoclonal immunoglobulins in promoting osteoclast differentiation and bone loss in patients with myeloma. These data help explain why bone loss is such a common feature in these patients and may lead to new therapeutic options.

Glucocorticoids have been used for decades for hypereosinophilic disorders. Eosinopenia occurs within a few hours, but the molecular mechanisms behind the disappearance of eosinophils from blood circulation are poorly defined. Hong et al demonstrate that in macaques in vivo, rapid glucocorticoid-induced, CXCR4-mediated eosinophil homing to the bone marrow occurs, thereby explaining, at least in part, the clinical phenomenon.

Quebec platelet disorder is manifested by >100-fold–increased platelet stores of urokinase plasminogen activator (PLAU/uPA) and bleeding due to platelet-dependent, accelerated fibrinolysis. Liang and colleagues reveal that the causative 78-kb tandem duplication in the PLAU gene results in such massive upregulation of protein production through ectopic association of the tandem duplication with a megakaryocyte enhancer and loss of epigenetic silencing.

Nuclear receptor coactivator 4 (NCOA4) was first identified as an autophagic receptor for ferritin with a capacity to direct ferritin into autophagosomes destined for destruction in the lysosome. Now, Li et al show that NCOA4 is required to mobilize the iron stored in hepatocyte ferritin for stress erythropoiesis, for example, after acute blood loss. Their work also suggests a new mode of iron-dependent transcriptional regulation for NCOA4 that involves hypoxia-inducible factors 1 and 2 (HIF-1 and -2).