From clinic to laboratory: Signal transduction analysis and future applications

Abstract

Abstract Background: Epithelioid hemangioma (EH) of bone is a vascular neoplasm with a ubiquitous distribution, including bone and soft tissue. The clinical behavior of EH is complicated because of its multifocal presentation and rare lymph node involvement. To date, up to 25% EH of bone presents synchronous bone lesions and specific gene alterations. Recently, a novel and recurrent FOS gene rearrangement was present in nearly one third of EH across a variety of locations. Before the discovery of gene rearrangements specific to this rare entity, EH was often misdiagnosed as epithelioid hemangioendothelioma (EHE) or angiosarcoma. Acute Myeloid Leukemia (AML) is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation, frequently resulting in impaired hematopoietic differentiation that results in granulocytopenia, thrombocytopenia or anemia, with or without leukocytosis. Currently, Azacitidine is the first-line clinical drug for both MDS and AML, whereas Venetoclax is mainly used for chronic lymphocytic leukemia (CLL) patients with or without 17p deletion. The combination of Venetoclax with Azacitidine is being tested with positive clinical results in AML therapy. However, the molecular mechanisms underlying the effect of this combination therapy are still unclear. Therefore, in this study we analyzed the molecular effects of Azacitidine and Venetoclax combination on the nuclear inositide-dependent pathways, mainly focus on PLC-β1. Aim: This study aimed at describing for the first time a metachronous multifocal lesions case of EH with fatal outcome and analyze the role of inositide pathways in AML.