Abstract：
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.
摘要：
尽管在治疗慢性淋巴细胞白血病（CLL）方面取得了重大进展，对治疗的抵抗仍然具有挑战性。NOTCH1激活,在CLL中常见，预后不良。本研究探讨了NOTCH1信号传导对维奈托克体外敏感性的影响。尽管NOTCH1激活对CLL细胞对维奈托克的敏感性有最小的损害，体外细胞竞争研究表明，在持续的venetoclax暴露下，具有组成型NOTCH1激活的细胞比野生型细胞长。我们的研究结果表明，虽然NOTCH1激活不足以赋予维奈托克难治性，具有NOTCH1激活的细胞逃逸并因此对维奈托克完全耐药的潜力增强。
