About this Research Topic
The Notch family consists of four Notch receptors (Notch1-4) and five ligands from the Delta-like and Jagged families (DLL1, DLL3, DLL4, JAG1 and JAG2). The Notch signaling cascade plays a key role in the regulation of processes including cell differentiation, and influences lineage decisions within the hematopoietic and immune systems. As such, significant research has been focused on elucidating the role of Notch signaling in the pathophysiology of hematologic malignancies, and its potential as a therapeutic target.
Notch 1 plays a key role in T-cell development, and its role in T-cell acute lymphoblastic leukemia (T-ALL) has been explored in several studies since the discovery that (7;9) translocation disrupts the Notch 1 gene. Mutations in the Notch 1 gene have been reported in around 60% of T-ALL cases, and the therapeutic potential of Notch 1 blocking molecules, such as γ-secretase inhibitors (GSIs), is under investigation. So far, low efficacy has been reported with the use of GSIs in T-ALL patients in early clinical trials, and severe gastrointestinal treatment-related adverse events pose a challenge.
Notch signaling has also been indicated to have a role in the pathophysiology of chronic lymphocytic leukemia (CLL). Genomic studies have identified the presence of mutations in the Notch 1 gene amongst a significant proportion of patients with CLL, and have been shown to correlate with more advanced disease and higher risk of transformation to diffuse large B-cell lymphoma (DLBCL).
This Research Topic aims to collate novel research contributing to advancing our understanding of the Notch signaling cascade and its role in the pathophysiology of lymphoid malignancies. The collection also welcomes manuscripts exploring novel therapeutic targets for the treatment of lymphoid malignancies in and upstream of the Notch 1 pathways.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Notch 1 plays a key role in T-cell development, and its role in T-cell acute lymphoblastic leukemia (T-ALL) has been explored in several studies since the discovery that (7;9) translocation disrupts the Notch 1 gene. Mutations in the Notch 1 gene have been reported in around 60% of T-ALL cases, and the therapeutic potential of Notch 1 blocking molecules, such as γ-secretase inhibitors (GSIs), is under investigation. So far, low efficacy has been reported with the use of GSIs in T-ALL patients in early clinical trials, and severe gastrointestinal treatment-related adverse events pose a challenge.
Notch signaling has also been indicated to have a role in the pathophysiology of chronic lymphocytic leukemia (CLL). Genomic studies have identified the presence of mutations in the Notch 1 gene amongst a significant proportion of patients with CLL, and have been shown to correlate with more advanced disease and higher risk of transformation to diffuse large B-cell lymphoma (DLBCL).
This Research Topic aims to collate novel research contributing to advancing our understanding of the Notch signaling cascade and its role in the pathophysiology of lymphoid malignancies. The collection also welcomes manuscripts exploring novel therapeutic targets for the treatment of lymphoid malignancies in and upstream of the Notch 1 pathways.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Keywords: Notch, chronic lymphocytic leukemia, hematologic malignancies
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
