Table of Contents
Goldenberg and colleagues' retrospective analysis of pediatric patients with high-risk, occlusive lower extremity deep vein thrombosis (DVT) suggests that thrombolytic therapy with tPA (with or without mechanical thrombolysis) may decrease the risk of postthrombotic syndrome (PTS).
In this issue of Blood, Wagner-Ballon and colleagues provide new insights into the pathogenesis of myelofibrosis with myeloid metaplasia (MMM) and a targeted therapeutic approach of NF-κB inhibition with the proteosome inhibitor bortezomib.
Dok-3 serves as an inhibitory adaptor protein through recruitment of the 5′-inositol phosphatase, SHIP-1. Ng and colleagues have generated a Dok-3–deficient mouse that exhibits hyperresponsive B cells, thereby implicating the adaptor as an important negative regulator of certain signaling events downstream from the antigen receptor.
Chinen and colleagues describe the outcome of gene therapy for 3 young adolescents with XSCID for whom prior attempts at allogeneic bone marrow transplant had failed to achieve significant immunologic reconstitution. Clear-cut clinical benefits have recently been obtained in multiple trials of gene therapy using hematopoietic stem cells (HSCs) for infants with XSCID and adenosine deaminase (ADA)-deficient SCID, and for young adults with chronic granulomatous disease (CGD). Thus, the debate over gene therapy has moved from “will it ever be beneficial?” to “when is it beneficial?” Studies are moving forward exploring the use of gene-corrected autologous HSCs in treating other immune deficiencies (eg, Wiskott-Aldrich syndrome), hemoglobinopathies, leukodystrophies, and mucopolysaccharidoses, as well as multiple applications to oncological diseases.
Mutations in the MYH9 gene give rise to May-Hegglin and related giant-platelet syndromes. In this issue of Blood, Chen and colleagues use mouse models to show that Myh9 acts through the Rho-ROCK pathway as a negative regulator of platelet production in the bone marrow.
In this issue of Blood, Svegliati and colleagues provide new insights into the mechanisms of chronic GVHD development by demonstrating the presence and functional activity of stimulatory anti–PDGF-R autoantibodies in patients with extensive chronic GVHD.
REVIEW IN TRANSLATIONAL HEMATOLOGY
HOW I TREAT
CHEMOKINES, CYTOKINES, AND INTERLEUKINS
Proteolytic processing of CXCL11 by CD13/aminopeptidase N impairs CXCR3 and CXCR7 binding and signaling and reduces lymphocyte and endothelial cell migration
CLINICAL TRIALS AND OBSERVATIONS
Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation
Clinical Trials & Observations
A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARα transcript after consolidation therapy: The Japan Adult Leukemia Study Group (JALSG) APL97 study
Clinical Trials & Observations
Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Tumor cell–associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell–dependent and–independent mechanisms
Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities
Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation
Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway
The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients
Proteasome inhibitor bortezomib impairs both myelofibrosis and osteosclerosis induced by high thrombopoietin levels in mice
Different STAT-3 and STAT-5 phosphorylation discriminates among Ph-negative chronic myeloproliferative diseases and is independent of the V617F JAK-2 mutation
Leukemic blasts in transformed JAK2-V617F–positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation.
Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission
Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning
Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value.
Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques.
CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors.
Transmission EM of macrophages infected with HIV-1 for 10 days demonstrating intracellular budding and accumulation of virions. See the related article by Peng et al, beginning on page 393.
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