<b>Figure 1. </b>Functional landscape of ABL N-Lobe

<p dir="ltr">We employed deep mutational scanning to map the functional landscape of the ABL N-lobe using the IL-3 dependent Ba/F3 cell line. Ba/F3 cells require IL-3 for survival, but this dependence is overcome by active kinases like BCR-ABL, providing a selection system for functi...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Ivan Sokirniy (21674222) (author)
مؤلفون آخرون: Haider Inam (21656565) (author), Marta Tomaszkiewicz (7184327) (author), Joshua Reynolds (17811456) (author), David McCandlish (5642495) (author), Justin Pritchard (14099750) (author)
منشور في: 2025
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الملخص:<p dir="ltr">We employed deep mutational scanning to map the functional landscape of the ABL N-lobe using the IL-3 dependent Ba/F3 cell line. Ba/F3 cells require IL-3 for survival, but this dependence is overcome by active kinases like BCR-ABL, providing a selection system for functional variants.</p><p dir="ltr">A comprehensive BCR-ABL mutant library was introduced into Ba/F3 cells. Following enrichment, the cells were grown for six days without IL-3, selecting for functional BCR-ABL mutants that promote growth factor-independent survival.</p><p dir="ltr">To quantify the effect of each mutation, we sequenced the mutant library before and after IL-3 withdrawal. This comparison allowed us to determine a functional score for each variant, revealing which mutations were deleterious to BCR-ABL's transformative capacity.</p>