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• W2928495578 abstract "Abstract Targeted sequencing of 103 leukemia-associated genes in leukemia cells from 841 treatment-naive patients with chronic lymphocytic leukemia (CLL) identified 89 (11%) patients as having CLL cells with mutations in genes encoding proteins that putatively are involved in hedgehog (Hh) signaling. Consistent with this finding, there was a significant association between the presence of these mutations and the expression of GLI1 (χ2 test, P &lt; .0001), reflecting activation of the Hh pathway. However, we discovered that 38% of cases without identified mutations also were GLI1+. Patients with GLI1+ CLL cells had a shorter median treatment-free survival than patients with CLL cells lacking expression of GLI1 independent of IGHV mutation status. We found that GANT61, a small molecule that can inhibit GLI1, was highly cytotoxic for GLI1+ CLL cells relative to that of CLL cells without GLI1. Collectively, this study shows that a large proportion of patients have CLL cells with activated Hh signaling, which is associated with early disease progression and enhanced sensitivity to inhibition of GLI1." @default.
• W2928495578 created "2019-04-11" @default.
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• W2928495578 date "2019-06-20" @default.
• W2928495578 modified "2023-10-16" @default.
• W2928495578 title "Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia" @default.
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• W2928495578 doi "https://doi.org/10.1182/blood-2018-09-873695" @default.
• W2928495578 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6587306" @default.
• W2928495578 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30923040" @default.
• W2928495578 hasPublicationYear "2019" @default.
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