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INSIDE BLOOD

IMMUNOBIOLOGY

The OX40 T-cell costimulatory molecule, critical for both survival and proliferation of activated T cells, has now been identified as a key negative regulator of Foxp3+ T regulatory cells (Tregs).

NEOPLASIA

Zhao and colleagues report on a novel small modular immunopharmaceutical (SMIP) directed against CD37 in chronic lymphocytic leukemia (CLL). This agent offers several potential design advantages, and demonstrates interesting preclinical activity through mechanisms of action different from standard therapies.

HEMOSTASIS

Cells use receptor-ligand interactions and endocrine, paracrine, and juxtacrine mechanisms to transmit signals to one another. Deregibus and colleagues now report that information transfer between cells also occurs through horizontal transfer of mRNA-rich microvesicles (MVs).

IMMUNOBIOLOGY

In this issue of Blood, Hatjiharissi and colleagues demonstrate that variability in NK-cell activity among individuals expressing different FcγRIIIa polymorphisms may result from variability in levels of receptor expression and not strictly from differences in receptor affinity, as was previously thought. These results have important implications for our ability to predict patient response to antibody-based therapeutics, as well as for our ability to design strategies to improve these drugs.

TRANSPLANTATION

Can cells from allogeneic blood and marrow transplants contribute to the formation of nonhematopoietic tissues? The report by Imanishi and colleagues in this issue of Blood indicates that they do. Using short tandem repeat analysis, these researchers found substantial amounts (9%-72%) of donor DNA occurring in fingernail clippings from 9 of 21 recipients 2 years and more after transplantation.

IMMUNOBIOLOGY

Recent notions of the immune response focus on the idea that innate pathogen recognition receptors (PRRs) lead to adaptive immune responses.

NEOPLASIA

LSCs make up a critical, but very rare, population that is very difficult to study in vivo. Neering and colleagues developed a unique mouse model system in which the properties of human LSCs are closely mimicked during CML development.

TRANSPLANTATION

Bernaudin and colleagues report, in this issue of Blood, the long-term results of the largest study of related myeloablative stem-cell transplantation for sickle cell disease (SCD). Their results show that slow, steady improvements over time, along with the addition of rabbit anti–thymocyte globulin (ATG) to the conditioning regimen, combine to produce an event-free survival (EFS) of 95.3%. They argue that for children with a suitable sibling-matched donor, myeloablative transplantation should be considered the standard of care in those at high risk for stroke.

HEMOSTASIS

Lacroix and colleagues provide the first evidence that endothelium-derived microparticles provide an efficient surface for plasminogen activation in a urokinase-type plasminogen activator (uPA)–dependent and uPA receptor (uPAR)–dependent manner, and suggest that generated plasmin may influence angiogenesis.

RED CELLS

Erythropoietin and the erythropoietin receptor have been cloned and studied in a lower vertebrate species. Key aspects of their structure and function have been evolutionarily conserved.

NEOPLASIA

Patients with monoclonal gammopathy of undetermined significance (MGUS) are at continuous risk of progression. Each year, 1% progress, usually to active multiple myeloma (MM).1  Such patients must be monitored for life. Asymptomatic smoldering multiple myeloma (SMM) has an even greater risk of progression to MM. Recently reported strategies improve our ability to estimate the risk of MM in these patients.

NEOPLASIA

In this issue of Blood, Spaulding and colleagues show that Lef-1, one of the transcription factors mediating Wnt signaling, is a transcriptional target of Notch in T-cell lymphomas. Notch-activating mutations are commonly found in human T-lineage acute lymphoblastic leukemia (T-ALL) cases, while activation of Wnt/β-catenin signaling has recently been shown to induce T-cell leukemia in mice. The proposed regulation of Lef-1 transcription by Notch suggests the intriguing possibility that the Notch and Wnt pathways are closely intertwined in the etiology of T-cell leukemia.

HEMOSTASIS

Redecha and colleagues demonstrate a requirement for both tissue factor and complement in this elegant investigation into the mechanisms of aPL-associated fetal loss.

BLOOD WORK

PLENARY PAPERS

PERSPECTIVE

REVIEW ARTICLES

REVIEW IN TRANSLATIONAL HEMATOLOGY

HOW I TREAT

CHEMOKINES, CYTOKINES, AND INTERLEUKINS

CLINICAL TRIALS AND OBSERVATIONS

GENE THERAPY

HEMATOPOIESIS

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

IMMUNOBIOLOGY

NEOPLASIA

PHAGOCYTES

STEM CELLS IN HEMATOLOGY

RED CELLS

TRANSFUSION MEDICINE

TRANSPLANTATION

CORRESPONDENCE

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