FLT3-regulated antigens as targets for leukemia-reactive cytotoxic T lymphocytes

The FMS-like tyrosine kinase 3 (FLT3) is highly expressed in acute myeloid leukemia (AML). Internal tandem duplications (ITD) of the juxtamembrane domain lead to the constitutive activation of the FLT3 kinase inducing the activation of multiple genes, which may result in the expression of leukemia-associated antigens (LAAs). We analyzed the regulation of LAA in FLT3-wild-type (WT)- and FLT3-ITD+ myeloid cells to identify potential targets for antigen-specific immunotherapy for AML patients. Antigens, such as PR-3, RHAMM, Survivin, WT-1 and PRAME, were upregulated by constitutively active FLT3-ITD as well as FLT3-WT activated by FLT3 ligand (FL). Cytotoxic T-cell (CTL) clones against PR-3, RHAMM, Survivin and an AML-directed CTL clone recognized AML cell lines and primary AML blasts expressing FLT3-ITD, as well as FLT3-WT+ myeloid dendritic cells in the presence of FL. Downregulation of FLT3 led to the abolishment of CTL recognition. Comparing our findings concerning LAA upregulation by the FLT3 kinase with those already made for the Bcr-Abl kinase, we found analogies in the LAA expression pattern. Antigens upregulated by both FLT3 and Bcr-Abl may be promising targets for the development of immunotherapeutical approaches against myeloid leukemia of different origin

Role of phason-defects on the conductance of a 1-d quasicrystal

We have studied the influence of a particular kind of phason-defect on the Landauer resistance of a Fibonacci chain. Depending on parameters, we sometimes find the resistance to decrease upon introduction of defect or temperature, a behavior that also appears in real quasicrystalline materials. We demonstrate essential differences between a standard tight-binding model and a full continuous model. In the continuous case, we study the conductance in relation to the underlying chaotic map and its invariant. Close to conducting points, where the invariant vanishes, and in the majority of cases studied, the resistance is found to decrease upon introduction of a defect. Subtle interference effects between a sudden phason-change in the structure and the phase of the wavefunction are also found, and these give rise to resistive behaviors that produce exceedingly simple and regular patterns.Comment: 12 pages, special macros jnl.tex,reforder.tex, eqnorder.tex. arXiv admin note: original tex thoroughly broken, figures missing. Modified so that tex compiles, original renamed .tex.orig in source