(WASHINGTON) – In 2012 Blood, the official journal of the American Society of Hematology (ASH), maintained its position as the most cited peer-reviewed publication in the field of hematology, publishing manuscripts detailing the most exciting basic, clinical, and translational hematology research breakthroughs.
To commemorate the 2012 achievements of the field and of the Blood journal, outgoing editor-in-chief Cynthia E. Dunbar, MD, senior investigator at the National Institutes of Health and head of the Molecular Hematopoiesis Section of the National Heart, Lung, and Blood Institute, who served as Blood editor from 2008-2012, has identified several manuscripts as the best of 2012 in the following categories:
2012 “Best of Blood” Editor-In-Chief Selections
Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex, Kurowska et al.
This study identifies a critical molecular complex involved in cytotoxic lymphocyte killing of tumors and virally-infected cells. Researchers examined the roles of cellular proteins including Rab27a and Slp in lytic granular trafficking, exocytosis, and the immune synapse. The results provide potential future targets to enhance or block cytotoxic T-cell and natural killer cell function.
IMMUNOBIOLOGY/THROMBOSIS AND HEMOSTASIS
Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates, Pandrea et al.
Highly active anti-retroviral therapy has shifted the spectrum of disease in HIV-infected patients away from infection and malignancies towards atherosclerosis and vascular pathology. This manuscript reports the development of a non-human primate simian immunodeficiency virus (SIV) model and clearly demonstrates the role of immune activation and intestinal microbial translocation in the pathophysiology of SIV/HIV-related vascular disease. The results suggest therapeutic approaches to avoid these complications and provide investigators with a disease model for preclinical testing. In addition to the above manuscript, read more about this work in a recent Blood press release.
Transmaternal cell flow leads to antigen-experienced cord blood, Dierselhuis et al.
The results of this study provide evidence that transmaternal cell flow and microchimerism remaining from prior pregnancies result in antigen-experienced umbilical cord blood T cells. These seminal observations have potential implications for choice of cord blood grafts and help explain birth order effects in sibling allotransplantation.
Zebrafish screen identifies novel compound with selective toxicity against leukemia, Ridges et al.
This study describes the first use of a zebrafish screening process to identify potential novel anti-cancer therapies, specifically the compound Lenaldekar, to target immature T-lymphoblasts, holding promise for utilization in T cell acute lymphocytic leukemias (ALL).
Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma, Kridel et al.
NOTCH1 mutations in CLL associated with trisomy 12, Balatti et al.
In these two studies, researchers identify recurrent NOTCH1 mutations via genome sequencing of tumor samples from patients with mantle cell lymphoma and from patients with chronic lymphocytic leukemia (CLL), specifically those with aggressive trisomy 12-associated CLL. The results suggest that targeted anti-NOTCH therapies should be investigated in these patient populations.
CLINICAL TRIALS AND OBSERVATIONS/GENE THERAPY/LYMHOID NEOPLASIA
The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis, Morgan et al.
This large randomized multiple myeloma trial demonstrates a progression-free survival advantage for thalidomide maintenance therapy following intensive or non-intensive induction therapy. Additionally, improved overall survival was demonstrated in patients with favorable but not with unfavorable interphase fluorescent in situ hybridization chromosomal tumor cell profiles.
B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells, Kochenderfer et al.
This is the largest trial to date of chimeric antigen receptor (CAR) genetically modified anti-CD19 T cells to treat refractory, chronic B-cell tumors. In the trial, this powerful novel therapy was associated with a complete response in one patient, partial responses in five patients, prolonged depletion of normal B cells, and reversible cytokine-associated toxicities.
Chronic myelogenous leukemia stem and progenitor cells demonstrate chromosomal instability related to repeated breakage-fusion-bridge cycles mediated by increased nonhomologous end joining, Chakraborty et al.
The results from this work offer new insights into the mechanisms of chromosomal instability in chronic myeloid leukemia (CML) progenitors, showing continued generation of unstable chromosomal lesions through repeated cycles of breakage and repair, and persistence of unstable aberrations in leukemic as compared to normal hematopoietic progenitors.
Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis, Makishima et al.
Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes, Damm et al.
SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes, Visconte et al.
These three complementary studies demonstrate the high frequency of somatic mutations in genes of spliceosome machinery in patients with myelodysplasia. The SF3B1 gene in particular is mutated in refractory anemia with ringed sideroblasts, has a positive prognostic impact, and inhibition of the spliceosome with an inhibitor can induce formation of ringed sideroblasts in cultured normal bone marrow cells, linking the spliceosome mutations causally to ringed sideroblast formation.
Rational design and characterization of platelet factor 4 antagonists for the study of heparin-induced thrombocytopenia, Sachais et al.
In this study, investigators design and characterize platelet factor 4 antagonists. These antagonists permit detailed investigation of the pathophysiology of heparin-induced thrombocytopenia (HIT) and are a step toward targeted therapy for this serious disorder.
Succeeding Dr. Dunbar as Blood editor-in-chief is Bob Lӧwenberg, MD, PhD, Professor of Hematology at Erasmus University Medical School, Rotterdam, the Netherlands. Dr. Lӧwenberg is the journal’s first non-North-American editor-in-chief. Another first for 2013 is the addition of the journal’s first-ever deputy editor, Nancy Berliner, MD, Chief of Hematology at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School in Boston. Drs. Lӧwenberg and Berliner assumed their positions on January 1.
If you would like a PDF copy of any of the manuscripts highlighted above, please email email@example.com.
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.
Blood® is a registered trademark of the American Society of Hematology.
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