Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed

Initial clustering - a key factor for phase separation kinetics in Fe-Cr-based alloys

Clustering of alloying elements in solution-treated Fe-Cr-based alloys is of considerable importance for their microstructure stability upon aging. The clustering of Cr after solution treatment in three stainless steel alloy categories has been studied by atom probe tomography. Furthermore, phase-field simulations are applied to examine the effect of initial clustering on phase separation evolution. It is concluded that the clustering of Cr found in solution-treated ferritic and duplex alloys plays a critical role in the nanostructure evolution during aging