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BLOOD COMMENTARIES

PLENARY PAPER

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.

REVIEW ARTICLE

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.

CLINICAL TRIALS AND OBSERVATIONS

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.

IMMUNOBIOLOGY AND IMMUNOTHERAPY

Sujal Ghosh,on behalf of the Inborn Errors Working Party of ESID and EBMT,Sevgi Köstel Bal,on behalf of the Inborn Errors Working Party of ESID and EBMT,Emily S. J. Edwards,on behalf of the Inborn Errors Working Party of ESID and EBMT,Bethany Pillay,on behalf of the Inborn Errors Working Party of ESID and EBMT,Raúl Jiménez Heredia,on behalf of the Inborn Errors Working Party of ESID and EBMT,Funda Erol Cipe,on behalf of the Inborn Errors Working Party of ESID and EBMT,Geetha Rao,on behalf of the Inborn Errors Working Party of ESID and EBMT,Elisabeth Salzer,on behalf of the Inborn Errors Working Party of ESID and EBMT,Samaneh Zoghi,on behalf of the Inborn Errors Working Party of ESID and EBMT,Hassan Abolhassani,on behalf of the Inborn Errors Working Party of ESID and EBMT,Tooba Momen,on behalf of the Inborn Errors Working Party of ESID and EBMT,Emma Gostick,on behalf of the Inborn Errors Working Party of ESID and EBMT,David A. Price,on behalf of the Inborn Errors Working Party of ESID and EBMT,Yu Zhang,on behalf of the Inborn Errors Working Party of ESID and EBMT,Andrew J. Oler,on behalf of the Inborn Errors Working Party of ESID and EBMT,Claudia Gonzaga-Jauregui,on behalf of the Inborn Errors Working Party of ESID and EBMT,Baran Erman,on behalf of the Inborn Errors Working Party of ESID and EBMT,Ayse Metin,on behalf of the Inborn Errors Working Party of ESID and EBMT,Inci Ilhan,on behalf of the Inborn Errors Working Party of ESID and EBMT,Sule Haskologlu,on behalf of the Inborn Errors Working Party of ESID and EBMT,Candan Islamoglu,on behalf of the Inborn Errors Working Party of ESID and EBMT,Kubra Baskin,on behalf of the Inborn Errors Working Party of ESID and EBMT,Serdar Ceylaner,on behalf of the Inborn Errors Working Party of ESID and EBMT,Ebru Yilmaz,on behalf of the Inborn Errors Working Party of ESID and EBMT,Ekrem Unal,on behalf of the Inborn Errors Working Party of ESID and EBMT,Musa Karakukcu,on behalf of the Inborn Errors Working Party of ESID and EBMT,Dagmar Berghuis,on behalf of the Inborn Errors Working Party of ESID and EBMT,Theresa Cole,on behalf of the Inborn Errors Working Party of ESID and EBMT,Aditya K. Gupta,on behalf of the Inborn Errors Working Party of ESID and EBMT,Fabian Hauck,on behalf of the Inborn Errors Working Party of ESID and EBMT,Hubert Kogler,on behalf of the Inborn Errors Working Party of ESID and EBMT,Andy I. M. Hoepelman,on behalf of the Inborn Errors Working Party of ESID and EBMT,Safa Baris,on behalf of the Inborn Errors Working Party of ESID and EBMT,Elif Karakoc-Aydiner,on behalf of the Inborn Errors Working Party of ESID and EBMT,Ahmet Ozen,on behalf of the Inborn Errors Working Party of ESID and EBMT,Leo Kager,on behalf of the Inborn Errors Working Party of ESID and EBMT,Dirk Holzinger,on behalf of the Inborn Errors Working Party of ESID and EBMT,Michael Paulussen,on behalf of the Inborn Errors Working Party of ESID and EBMT,Renate Krüger,on behalf of the Inborn Errors Working Party of ESID and EBMT,Roland Meisel,on behalf of the Inborn Errors Working Party of ESID and EBMT,Prasad T. Oommen,on behalf of the Inborn Errors Working Party of ESID and EBMT,Emma Morris,on behalf of the Inborn Errors Working Party of ESID and EBMT,Benedicte Neven,on behalf of the Inborn Errors Working Party of ESID and EBMT,Austen Worth,on behalf of the Inborn Errors Working Party of ESID and EBMT,Joris van Montfrans,on behalf of the Inborn Errors Working Party of ESID and EBMT,Pieter L. A. Fraaij,on behalf of the Inborn Errors Working Party of ESID and EBMT,Sharon Choo,on behalf of the Inborn Errors Working Party of ESID and EBMT,Figen Dogu,on behalf of the Inborn Errors Working Party of ESID and EBMT,E. Graham Davies,on behalf of the Inborn Errors Working Party of ESID and EBMT,Siobhan Burns,on behalf of the Inborn Errors Working Party of ESID and EBMT,Gregor Dückers,on behalf of the Inborn Errors Working Party of ESID and EBMT,Ruy Perez Becker,on behalf of the Inborn Errors Working Party of ESID and EBMT,Horst von Bernuth,on behalf of the Inborn Errors Working Party of ESID and EBMT,Sylvain Latour,on behalf of the Inborn Errors Working Party of ESID and EBMT,Maura Faraci,on behalf of the Inborn Errors Working Party of ESID and EBMT,Marco Gattorno,on behalf of the Inborn Errors Working Party of ESID and EBMT,Helen C. Su,on behalf of the Inborn Errors Working Party of ESID and EBMT,Qiang Pan-Hammarström,on behalf of the Inborn Errors Working Party of ESID and EBMT,Lennart Hammarström,on behalf of the Inborn Errors Working Party of ESID and EBMT,Michael J. Lenardo,on behalf of the Inborn Errors Working Party of ESID and EBMT,Cindy S. Ma,on behalf of the Inborn Errors Working Party of ESID and EBMT,Tim Niehues,on behalf of the Inborn Errors Working Party of ESID and EBMT,Asghar Aghamohammadi,on behalf of the Inborn Errors Working Party of ESID and EBMT,Nima Rezaei,on behalf of the Inborn Errors Working Party of ESID and EBMT,Aydan Ikinciogullari,on behalf of the Inborn Errors Working Party of ESID and EBMT,Stuart G. Tangye,on behalf of the Inborn Errors Working Party of ESID and EBMT,Arjan C. Lankester,on behalf of the Inborn Errors Working Party of ESID and EBMT,Kaan Boztug,on behalf of the Inborn Errors Working Party of ESID and EBMT

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.

LYMPHOID NEOPLASIA

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.

PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS

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.

PLATELETS AND THROMBOPOIESIS

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.

RED CELLS, IRON, AND ERYTHROPOIESIS

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).

THROMBOSIS AND HEMOSTASIS

LETTER TO BLOOD

BLOOD WORK

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