(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email email@example.com.
Cardiovascular toxicity and titin cross-reactivity of affinity enhanced T cells in myeloma and melanoma, Linette et al.
While the successful genetic engineering of T cells to express T cell receptors (TCR) with high affinity and specificity for antigen has ushered active interest in the development of cancer immunotherapy, toxicities associated with this procedure are still being uncovered. A manuscript appearing this week in Blood describes fatal cardiovascular toxicity occurring in two patients treated with lymphocytes engineered to express affinity-enhanced TCR specific for MAGE-A3 and restricted in human leukocyte antigen A1. While these toxicities could not be predicted from current preclinical studies, in this manuscript, as part of an extensive investigation, researchers identified a titin-derived peptide expressed in cardiomyocytes and recognized by the transgenic TCR as the cause of the toxicity. This highly relevant finding reinforces the necessity of discussing novel approaches to predict and prevent toxicity associated with the rapidly evolving practice of adoptive T-cell therapy with genetically engineered lymphocytes.
European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013, Baccarani et al.
Recommendations from the European LeukemiaNet have been influential worldwide for the therapeutic management of patients with chronic myeloid leukemia (CML). This eagerly anticipated update published in this week’s issue of Blood considers new findings, particularly on the impact of second-generation tyrosine kinase inhibitors, and provides guidance for when and how to change therapies depending on various levels of drug response.
Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients, Loïc Garçon et al.
Diamond Blackfan Anemia (DBA) is a congenital disorder characterized by erythroid hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous mutations in genes that encode ribosomal proteins, yet understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. A manuscript in this week’s issue of Blood presents the first report regarding induced pluripotent stem cells (iPSCs) derived from DBA patients. The data show that DBA iPSCs recapitulate hematopoietic phenotypes relevant to the disease, including defective ribosomal subunit assembly and hematopoietic differentiation, which are at least partially reversed by ectopic expression of RPS19 or RPL5 complementary DNA. These cells provide an important new model for the study of DBA.
Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling, Locatelli et al.
In this week’s issue of Blood, investigators report on the largest number of children to date (485 cases) with thalassemia major or sickle cell disease who are undergoing sibling-matched transplantation. This manuscript represents both Eurocord registry data and Oakland registry data that have been combined to provide a cumulative evaluation of various details of transplant and disease outcome in children who have received a sibling-matched transplantation either through bone marrow (BMT) or cord blood (CBT). The data collected during the last 20 years demonstrate six-year overall survival results of 95 percent with a median follow up of 70 months after matched sibling transplants, regardless of stem cell source. The six-year disease-free survival rates for various subgroups varied between 80 percent and 90 percent. The data underscore that these children have excellent outcomes after both human leukocyte antigen-identical sibling BMT and CBT.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
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