Mixed lineage leukemia (MLL) (KMT2A) rearrangements (KMT2Ar) play a crucial role in leukemogenesis. Dependent on age, major differences exist regarding disease frequency, main fusion partners and prognosis. In infants, up to 80% of acute lymphoid leukemia (ALL) bear a MLL translocation and half of them are t(4;11), resulting in a poor prognosis. In contrast, in adults only 10% of acute myeloid leukemia (AML) bear t(9;11) with an intermediate prognosis. The reasons for these differences are poorly understood. Recently, we established an efficient CRISPR/Cas9-based KMT2Ar model in hematopoietic stem and progenitor cells (HSPCs) derived from human cord blood (huCB) and faithfully mimicked the underlying biology of the disease. Here, we applied this model to HSPCs from adult bone marrow (huBM) to investigate the impact of the cell of origin and fusion partner on disease development. Both genome-edited infant and adult KMT2Ar cells showed monoclonal outgrowth with an immature morphology, myelomonocytic phenotype and elevated KMT2Ar target gene expression comparable to patient cells. Strikingly, all KMT2Ar cells presented with indefinite growth potential except for MLL-AF4 huBM cells ceasing proliferation after 80 days. We uncovered FFAR2, an epigenetic tumor suppressor, as potentially responsible for the inability of MLL-AF4 to immortalize adult cells under myeloid conditions.
Surprisingly, research on name discrimination in advertising is still at an early stage, although all flanking fields have experienced deep and broad research. Discrimination can be evoked through the use of names in advertising. In this article, the reader will learn which factors, such as stereotyping or serving stereotypes, have an influence on the perception in certain name bearers. This work makes a contribution to understanding and working through the problem in more detail. The use of names in advertising, which classify certain names and thus people into groups, may not be suitable if discrimination is to be excluded. The factors and individual interdependencies were only examined in this work in Germany and may therefore be different in other countries and cultures.
Digitalization poses great challenges for companies and especially for newspaper publishers. Due to the large number of digital competitors on the advertising market, media companies are forced to proactively win customers. A major German media company has thus dared to experiment and put the question of pricing for booking newspaper advertising in the hands of its customers. With the so-called "pay what you want" (PWYW) payment model, customers can be won and additional budgets spent. This paper explores the question of whether PWYW is a suitable sales model for newspaper companies and which factors have an influence. The results of the interviews with those involved show solutions, opportunities, problems and that additional turnover can be generated.
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