부산대학교 도서관

The range of active concentrations was in line with what is reported in T-ALL models.[6] CB-103 sensitive cell lines were then treated with another Notch inhibitor that had undergone early clinical development, the GSI crenigacestat (LY3039478).[9] CB-103 resulted overall superior in terms of antiproliferative activity and cell death (Figures S1 and S2). The other sensitive cell lines had mutations in genes involved in Notch pathway or mutated in the Notch-driven DLBCL clusters, but the contribution of the Notch-related mutations in the sensitivity cannot be clearly determined. Somatic mutations leading to activation of Notch signalling are recurrent in different blood cancers, including T-cell acute lymphoblastic leukaemia (T-ALL), chronic lymphocytic leukaemia (CLL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).[[1], [3]] In mature B-cell lymphomas, the mutations most commonly occur in NOTCH1 and NOTCH2 genes and less frequently in genes coding for negative regulators of the pathway (such as DTX1, SPEN, FBXW7, MAML2). [Extracted from the article]