CAD204520 Targets NOTCH1 PEST Domain Mutations in Lymphoproliferative Disorders.

ABSTRACT: NOTCH1 PEST domain mutations are often seen in hematopoietic malignancies, including T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). These mutations play a key role in the development and progression of lymphoproliferative tumors by increasing the Notch signaling and, consequently, promoting cell proliferation, survival, migration, and suppressing apoptosis. There is currently no specific treatment available for cancers caused by NOTCH1 PEST domain mutations. However, several NOTCH1 inhibitors are in development. Among these, inhibition of the Sarco-endoplasmic Ca²⁺-ATPase (SERCA) showed a greater effect in NOTCH1-mut

SUBMITTER: Pagliaro L 

PROVIDER: S-EPMC10815907 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature