PI3K/AKT signaling controls ICM maturation and proper epiblast and primitive endoderm specification in mice.

The inner cell mass (ICM) of early mouse embryos is specified into epiblast (Epi) and primitive endoderm (PrE) lineages during blastocyst formation. The antagonistic transcription factors (TFs) NANOG and GATA-binding protein 6 (GATA6) in combination with fibroblast growth factor (FGF)/extracellular-signal-regulated kinase (ERK) signaling are central actors in ICM fate choice. However, what initiates the specification of ICM progenitors into Epi or PrE and whether other factors are involved in this process has not been fully understood yet.

Lack of interferon-alpha-induced tyrosine phosphorylation of Vav proto-oncogene in patients with myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia (MMM) is an uncommon chronic myeloproliferative disorder characterized by clonal stem cell proliferation and reactive non-clonal proliferation of bone marrow fibroblasts with fibrosis. In the absence of curative therapy, the current management for the majority of patients is directed towards alleviation of symptoms and improvement in quality of life. A number of experimental therapies have been investigated, among which is the use of type I interferon (IFN)-alpha, whose overall results are disappointing.

p95(vav) associates with the type I interferon (IFN) receptor and contributes to the antiproliferative effect of IFN-alpha in megakaryocytic cell lines.

The vav proto-oncogene product is a 95 kDa protein predominantly expressed in hematopoietic cells. Vav presents a wide range of functional domains, including structural domains known to be involved in signal transduction. Triggering of various cytokine receptors among which type I interferon receptor induces a rapid and transient tyrosine phosphorylation of p95(vav).

Induction of macrophagic differentiation and cytokine secretion by IgG1 molecules in human normal monocytes and myelogenous leukemia cells.

A role for IgG molecules in the activation of human myelogenous leukemia cells was examined. When added to monoblastic (U937) leukemia cells, mouse (m)IgG1 produced a dose- and time-dependent inhibitory growth effect associated with the induction of morphological features characteristic of macrophage maturation, and enhanced surface expression of Mac-1/CD11b characteristic of monocyte development. A study of isotype dependency of mig indicated that the effect was specific for Ig molecules of the IgG1 and IgG2b subclasses, whereas IgG2a or IgM had no effect.