Issue Archive

Retroviral insertional mutagenesis screens have identified of dozens of potential leukemia/lymphoma genes in mice and rats. Sauvageau and colleagues suggest that proviral insertions may affect the expression of multiple nearby genes in leukemia cells, and that the genes affected may be cell-type dependent.

Analyzing hematopoiesis in the Ts65Dn mouse, which is trisomic for many orthologs of human chromosome 21 genes, may shed light on leukemogenesis in Down syndrome, as demonstrated by Kirsammer and colleagues in this issue.

Many functions have been suggested for the large amounts of thrombospondin-1 that are stored in α-granules of platelets. Isenberg et al describe a new role whereby thrombospondin-1 counteracts NO and allows platelet activation to take place in situations in which NO is being generated.

In this issue of Blood, Ruggeri and colleagues highlight the high risk of vascular events in patients with essential thrombocythemia and polycythemia vera undergoing operative procedures even with current “optimal” surgical prophylaxis.

In this issue of Blood, Shim and colleagues define a dual role for platelet glycoprotein (GP)Ibα (the major ligand-binding subunit of the GPIb-IX-V complex) in regulating ADAMTS13-mediated cleavage of von Willebrand factor (VWF) under shear: it alleviates an inhibitory effect of the VWF A1 domain on cleavage of the A2 domain,¹  and it allows tensile force to be exerted on the A2 domain through at least 2 platelets binding per VWF multimer via the A1 domain (see figure).

Thromboxane A₂ and ADP act as important feedback activators of platelet function. The secretion of neuropeptides reveals a novel feedback loop that is not targeted specifically by aspirin and clopidogrel.

Notch activation is an early and critical event during T-cell leukemogenesis, hence Notch signal inhibition is a desirable and feasible intervention to abrogate the process of lymphocyte accumulation and antibody production secondary to apoptosis defects as shown in 2 murine models here. However, prudent and diligent assessment of the risks and benefits of any such therapies should be imperative, especially in many nonmalignant lymphoproliferative and autoimmune disorders, including autoimmune lymphoproliferative syndrome (ALPS).

TGFβ has been considered the most likely ALK1 ligand related to hemorrhagic telangiectasia (HHT). New research reports that TGFβR2 and ALK5 are not required for HHT disease suggesting that HHT might not be a TGFβ subfamily disease.

Quinn and colleagues evaluate 3 early severity predictors defined from the Cooperative Study of Sickle Cell Disease in an independent prospective newborn cohort and find them unrelated to long-term adverse outcomes. Despite methodologic differences between the studies, the result calls into question the use of these markers for identification of transplant candidates.

In this issue of Blood, Dispenzieri and colleagues report that the serum immunoglobulin free light chain (FLC) ratio is an independent predictor for progression in patients with smoldering multiple myeloma.

Genome-wide studies reveal somatically acquired regions of uniparental isodisomy (UPD) in 25% of pediatric acute lymphoblastic leukemia (ALL). These regions probably contain tumor-suppressor genes involved in pathogenesis.

In this issue of Blood, Ephrem et al demonstrate that IVIg expands CD4⁺CD25⁺FoxP3⁺ T regulatory cells (Tregs) and enhances their function in vivo and in vitro. Their findings shed new light on the elusive mechanism of action of IVIg in ameliorating autoimmune diseases.

In this issue of Blood, Hitchcock and colleagues show that the nonreceptor tyrosine kinase FAK plays a critical role in regulating megakaryocyte maturation and platelet function in vivo.

In this issue of Blood, Ward and colleagues make some novel fundamental observations on the nature of the immune response during autoimmune hemolytic anemia (AIHA). They show a key role for T regulatory cells (Tregs) in the pathogenesis of this autoimmune disease.

The dose and schedule of an iron chelator, whether given parenterally or orally, is variable and depends on the rate of iron loading.