RESUMEN
Despite significant progress in treating chronic lymphocytic leukaemia (CLL), resistance to therapy remains challenging. NOTCH1 activation, common in CLL, confers adverse prognosis. This study explores the impact of NOTCH1 signalling on venetoclax sensitivity in vitro. Although NOTCH1 activation minimally impaired the susceptibility of CLL cells to venetoclax, ex vivo cell competition studies reveal that cells with constitutive NOTCH1 activation outgrew their wild-type counterparts in the presence of ongoing venetoclax exposure. Our findings suggest that while NOTCH1 activation is insufficient to confer venetoclax refractoriness, there is enhanced potential for cells with NOTCH1 activation to escape and thus become fully resistant to venetoclax.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinogénesis/patología , Linfoma/tratamiento farmacológico , Linfoma/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/deficiencia , Animales , Antineoplásicos/farmacología , Carcinogénesis/metabolismo , Muerte Celular/efectos de los fármacos , Estimación de Kaplan-Meier , Linfoma/metabolismo , Ratones Transgénicos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
A highly efficient synthetic method for the preparation of 2-aminobenzothiazoles starting from arylthioureas has been reported. By using a nickel catalyst, arylthioureas undergo intramolecular oxidative C-H bond functionalization, giving the desired 2-aminobenzothiazoles in good to excellent yields. This protocol features an inexpensive catalyst, low catalyst loading, mild reaction conditions, a short reaction time, and good to excellent yields, and it can be scaled up easily to a gram scale with almost no yields decreasing.