Magic™ Anti-MEK1/2 (Phospho T292) polyclonal antibody

Erdheim-Chester disease (ECD) is characterized by the infiltration of tissues by foamy CD68(+)CD1a(-) histiocytes, with 1500 known cases since 1930. Mutations activating the MAPK pathway are found in more than 80% of patients with ECD, mainly the BRAF(V600E) activating mutation in 57% to 70% of cases, followed by MAP2K1 in close to 20%. The discovery of BRAF mutations and of other MAP kinase pathway alterations, as well as the co-occurrence of ECD with LCH in 15% of patients with ECD, led to the 2016 revision of the classification of histiocytoses in which LCH and ECD belong to the "L" group. Both conditions are considered inflammatory myeloid neoplasms. Ten percent of ECD cases are associated with myeloproliferative neoplasms and/or myelodysplastic syndromes. Some of the most striking signs of ECD are the long bone involvement (80%-95%), as well as the hairy kidney appearance on computed tomography scan (63%), the coated aorta (40%), and the right atrium pseudo-tumoral infiltration (36%). Central nervous system involvement is a strong prognostic factor and independent predictor of death. Interferon-alpha seems to be the best initial treatment of ECD. Since 2012, more than 200 patients worldwide with multisystem or refractory ECD have benefitted from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have an overall, robust, and reproducible efficacy in ECD, with no acquired resistance to date, but their use may be best reserved for the most severe manifestations of the disease, as they may be associated with serious adverse effects and as-yet-unknown long-term consequences.

This study used qRT-PCR to examine variation in the expression of 13 myogenes during muscle development in four prenatal periods (21, 40, 70 and 90 days post-insemination) in commercial (the three-way Duroc, Landrace and Large-White cross) and local Piau pig breeds that differ in muscle mass. There was no variation in the expression of the CHD8, EID2B, HIF1AN, IKBKB, RSPO3, SOX7 and SUFU genes at the various prenatal ages or between breeds. The MAP2K1 and RBM24 genes showed similar expression between commercial and Piau pigs but greater expression (p < 0.05) in at least one prenatal period. Pair-wise comparisons of prenatal periods in each breed showed that only the CSRP3, LEF1, MRAS and MYOG genes had higher expression (p < 0.05) in at least one prenatal period in commercial and Piau pigs. Overall, these results identified the LEF1 gene as a primary candidate to account for differences in muscle mass between the pig breeds since activation of this gene may lead to greater myoblast fusion in the commercial breed compared to Piau pigs. Such fusion could explain the different muscularity between breeds in the postnatal periods.