Rabbit Anti-Human MEK1/MEK2 (phospho Ser221) monoclonal antibody, clone L.853.2

Histiocytic sarcoma in advanced clinical stages is typically an aggressive neoplasm, with poor response to conventional chemotherapy. An 18-year-old male with refractory histiocytic sarcoma that had transformed from Rosai-Dorfman disease was admitted to our hospital. A pathogenic variant of MAP2K1 was detected by next-generation sequencing of tumor specimens. Affected regions showed excellent responses to the MEK inhibitor trametinib. It has been reported that RAS/MEK/ERK pathway is activated in many cases of histiocytic sarcoma. MEK inhibition may represent a useful treatment option in histiocytic sarcoma.

The ERK/MAPK signalling cascade is involved in many cellular functions. In mice, the targeted ablation of genes coding for members of this pathway is often associated with embryonic death due to the abnormal development of the placenta. The placenta is essential for nutritional and gaseous exchanges between maternal and embryonic circulations, as well as for the elimination of metabolic waste. These exchanges occur without direct contact between the two circulations. In mice, the blood-placenta barrier consists of a triple layer of trophoblast cells adjacent to endothelial cells from the embryo. In the ERK/MAPK cascade, MEK1 and MEK2 are dual-specificity kinases responsible for the activation of the ERK1 and ERK2 kinases. Inactivation of Mek1 causes placental malformations resulting from defective proliferation and differentiation of the labyrinthine trophoblast cells and leading to a severe delay in the development and the vascularization of the placenta, which explains the embryonic death. Although Mek2(-/-) mutants survive without any apparent phenotype, a large proportion of Mek1(+/-) Mek2(+/-) double heterozygous mutants die during gestation from placenta anomalies affecting the establishment of the blood-placenta barrier. Together, these data reveal how crucial is the role of the ERK/MAPK pathway during the formation of the placenta. (C) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.