Abramspoole7265

Taken together, our results showed that ANXA1 could be used as a potential therapeutic target for inflammation-related neurodegenerative diseases.Inositol phosphates are water-soluble intracellular signaling molecules found in eukaryotes from yeasts to mammals, which are synthesized by a complex network of enzymes including inositol phosphate kinases. Among these, inositol polyphosphate multikinase (IPMK) is a promiscuous enzyme with broad substrate specificity, which phosphorylates multiple inositol phosphates, as well as phosphatidylinositol 4,5-bisphosphate. In addition to its catalytic actions, IPMK is known to non-catalytically control major signaling events via direct protein-protein interactions. In this review, we describe the general characteristics of IPMK, highlight its pleiotropic roles in various physiological and pathological conditions, and discuss future challenges in the field of IPMK signaling pathways.Next generation sequencing (NGS) technology has revealed the heterogeneity of diffuse large B-cell lymphoma (DLBCL) from a mutation perspective. Accordingly, the conventional cell of origin-based classification of DLBCL has changed to a mutation-based classification. Mutation analysis delineates that B-cell receptor pathway activation, EZH2 mutation, and NOTCH mutations are distinctive drivers of DLBCL. Moreover, the combination of RNA expression data and DNA mutation results suggests similarity between DLBCL subtypes and other non-Hodgkin lymphomas. NGS-based dissection of DLBCL would be the cornerstone for precision treatment in this heterogeneous disease in the near future.The goal of cancer immunotherapy is to restore and optimize the immune response against malignant clones through several stages, from recognition of tumor antigens to establishment of long-lived memory cell populations. Boosting the intrinsic anti-tumor immune responses of the patients' own, several types of "active immunotherapies" have been tried in many types of malignancies, inspired by successful experiences of immune checkpoint inhibition even in Hodgkin lymphoma. However, in B-cell non-Hodgkin lymphomas, clinical usefulness of such "active immunotherapies" is relatively unsatisfactory considering the remarkable advances in "passive immunotherapy," including CD19-targeting chimeric antigen receptor T-cell therapy. Understanding how tumor cells and immune cells interact and contribute to immune evasion processes in the tumor microenvironment (TME) is an important prerequisite for the successful restoration of anti-tumor immune responses. In this review, a recent understanding of the biology of the immune tumor microenvironment surrounding B-cell non-Hodgkin lymphomas will be introduced. In addition, novel therapeutic approaches targeting the immune microenvironment other than immune checkpoint blockade are discussed.Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder caused by the clonal expansion of myeloid precursors that differentiate into CD1a+/CD207+ cells in the lesion. Advances in genomic sequencing techniques have improved our understanding of the pathophysiology of LCH. Activation of the mitogen-activated protein kinase (MAPK) pathway is a key molecular mechanism involved in the development of LCH. Recurrent BRAF mutations and MAP2K1 mutations are the major molecular alterations involved in the activation of the MAPK pathway. Recent studies have supported the "misguided myeloid differentiation model" of LCH, where the extent of disease is defined by the differentiation stage of the cell in which the activating somatic MAPK mutation occurs, suggesting LCH. Several studies have advocated the efficacy of targeted therapy using BRAF inhibitors with a high response rate, especially in patients with high-risk or refractory LCH. However, the optimal treatment scheme for children remains unclear. This review outlines recent advances in LCH, focusing on understanding the molecular pathophysiology, emerging targeted therapy options, and their clinical implications.Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological neoplasms characterized by ineffective hematopoiesis, morphologic dysplasia, and cytopenia. MDS overlap syndromes include various disorders, such as myelodysplastic/myeloproliferative neoplasms and hypoplastic MDS with aplastic anemia characteristics. MDS overlap syndromes share the characteristics of other diseases, which make differential diagnoses challenging. MitoPQ Advances in genomic studies have led to the discovery of frequent mutations in MDS and overlap syndromes; however, most of the mutations are not specific for the diagnosis of these diseases. The molecular characteristics of the overlap syndromes usually do not show a just "in-between" form but rather heterogeneous features. Established diagnostic criteria for these diseases based on clinical, morphologic, and laboratory features are still useful when combined with genomic data. It is expected that further studies for MDS and overlap syndromes will place emphasis on the roles of mutations as therapeutic targets and prognostic indicators.Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell malignancies. Chronic inflammation and a dysregulated immune system are central to the pathogenesis and progression of MPNs. Interferon alpha (IFNα) was first used for the treatment of MPNs approximately 40 years ago. It has significant antiviral effects and plays a role in anti-proliferative, pro-apoptotic, and immunomodulatory responses. IFNα is an effective drug that can simultaneously induce significant rates of clinical, hematological, molecular, and histopathological responses, suggesting that the disease may be cured in some patients. However, its frequent dosage and toxicity profile are major barriers to its widespread use. Pegylated IFNα (peg-IFNα), and more recently, ropeginterferon alpha-2b (ropeg-IFNα-2b), are expected to overcome these drawbacks. The objective of this article is to discuss the clinical role of IFNα in Philadelphia-negative MPNs through a review of recent studies. In particular, it is expected that new IFNs, such as peg-IFNα and ropeg-IFNα-2b, with lower rates of discontinuation due to fewer adverse effects, will play important clinical roles.