The MLL-Menin Interaction is a Therapeutic Vulnerability in <em>NUP98</em>-rearranged AML

\ua9 2023 Wolters Kluwer Health. All rights reserved. Chromosomal translocations involving the NUP98 locus are among the most prevalent rearrangements in pediatric acute myeloid leukemia (AML). AML with NUP98 fusions is characterized by high expression of HOXA and MEIS1 genes and is associated with poor clinical outcome. NUP98 fusion proteins are recruited to their target genes by the mixed lineage leukemia (MLL) complex, which involves a direct interaction between MLL and Menin. Here, we show that therapeutic targeting of the Menin-MLL interaction inhibits the propagation of NUP98-rearrranged AML both ex vivo and in vivo. Treatment of primary AML cells with the Menin inhibitor revumenib (SNDX-5613) impairs proliferation and clonogenicity ex vivo in long-term coculture and drives myeloid differentiation. These phenotypic effects are associated with global gene expression changes in primary AML samples that involve the downregulation of many critical NUP98 fusion protein-target genes, such as MEIS1 and CDK6. In addition, Menin inhibition reduces the expression of both wild-type FLT3 and mutated FLT3-ITD, and in combination with FLT3 inhibitor, suppresses patient-derived NUP98-r AML cells in a synergistic manner. Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL-Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors

Epigenetic regulator genes direct lineage switching in MLL/AF4 leukaemia

The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukaemia. Relapse can be associated with a lineage switch from acute lymphoblastic to acute myeloid leukaemia resulting in poor clinical outcomes due to resistance towards chemo- and immuno-therapies. Here we show that the myeloid relapses share oncogene fusion breakpoints with their matched lymphoid presentations and can originate from varying differentiation stages from immature progenitors through to committed B-cell precursors. Lineage switching is linked to substantial changes in chromatin accessibility and rewiring of transcriptional programmes, including alternative splicing. These findings indicate that the execution and maintenance of lymphoid lineage differentiation is impaired. The relapsed myeloid phenotype is recurrently associated with the altered expression, splicing or mutation of chromatin modifiers, including CHD4 coding for the ATPase/helicase of the nucleosome remodelling and deacetylation complex, NuRD. Perturbation of CHD4 alone or in combination with other mutated epigenetic modifiers induces myeloid gene expression in MLL/AF4-positive cell models indicating that lineage switching in MLL/AF4 leukaemia is driven and maintained by disrupted epigenetic regulation

Survey of functional food market of baking products in Lower Silesia

Celem opracowania było przedstawienie rynku żywności funkcjonalnej na Dolnym Śląsku oraz przegląd produktów funkcjonalnych i ich producentów w aspekcie podstawowej definicji żywności funkcjonalnej. Charakterystyki dokonano, kładąc nacisk na najpopularniejszą z reprezentowanych w tym rejonie branż, tj. przemysł piekarski, starając się uwzględniać podział żywności ze względu na spełniane funkcje zdrowotne. Przedstawiono również przewidywaną strategię rozwoju tej branży do roku 2030, co wynikało z wymogów projektu, w ramach którego badania te prowadzono (Identyfikacja potencjału i zasobów Dolnego Śląska w obszarze nauka i technologia na rzecz poprawy jakości życia Quality of Life), oraz wytycznych przyszłych kierunków rozwoju.The aim of this study is to present the Lower Silesian functional food market and to conduct a survey of functional products and their producers, bearing in mind functional food’s definition, according to which: “Food might be considered functional if it beneficially affects one or more target functions in the body beyond adequate nutritional effects in a way that is relevant to either an improved state of health and well-being and/or reduction of risk of disease. It is consumed as part of a normal food pattern. It is not a pill, a capsule or any form of dietary supplement” [ftp://ftp.cordis.europa.eu…]. The characteristic has been prepared in accordance to the most popular branch among those represented in the region, i.e. the bakery industry, with acknowledgment of its division into particular health functions fulfilled: cholesterol-reducing ford, low-fat ford, low-carbohydrate ford, low-salt ford, vitaminenriched ford, fibre-enriched ford, ‘light’ food and high-protein food. The study includes also a prediction of the development strategy of this branch until the year 2030

Awareness, knowledge and frequency of consumption energy drinks and isotonic drinks by the young people, acttively training sports

Od kilku lat można zauważyć wzrost tendencji do spożywania napojów funkcjonalnych, w szczególności energetyzujących i izotonicznych. Światowe statystyki w tej kwestii są co najmniej niepokojące, gdyż w samych Stanach Zjednoczonych z roku na rok przybywa zwolenników tego typu produktów – nawet do 5% w skali roku, a w Polsce jest to już co trzecia osoba. Głównymi konsumentami tych napojów są przede wszystkim młodzi ludzie – core-consumers (15–25 lat – uczniowie i studenci) oraz metro consumers (25–35 lat – osoby młode, intensywnie pracujące) [Kopacz 2012]. Niniejsze badania zostały przeprowadzone w celu sprawdzenia stanu wiedzy młodych sportowców w zakresie spożywania tych napojów, z równoczesnym wskazaniem przez nich właściwości prozdrowotnych i zagrożeń, oraz określenie ich predyspozycji konsumpcyjnych w najbliższych latach.Consumption the functional drinks has been growing for past several years, especially energy and isotonic drinks. The world’s statistic is staggering, because only in the United States there are more supporters to buy this product every year – even up to 5%. In Poland, actually every third person buys this product. Main consumers of this beverages are the young people – “core consumers” (15–25 years – teenagers and students) and “metro consumers” (25–35 years – young, hardworking people). This research was taken to get some information about knowledge of functional drinks (especially energy ana isotonic drinks) among young sportspeople, showing their health benefits and threats and checking their predisposition to consume that drinks in the future