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Learn MoreT-cell acute lymphoblastic leukemia (T-ALL) is a highly malignant pediatric leukemia, where few therapeutic options are available for patients which relapse. The evolutionarily conserved Hedgehog (Hh) pathway plays a crucial role in patterning and organogenesis during early development, in adult tissue maintenance and repairing functions. Once Hh ligands bind to PTCH1/2 on target cells, the inhibition of Patched proteins for Smo is relieved. Smo translocates to the primary cilium and leads to the breakdown of a protein complex formed by Suppressor of Fused (SUFU) and GLI proteins. GLI transcription factors (GLI1-3) are released and translocate to the nucleus, initiating transcription of Hh target genes. GLI2 and GLI3 have transcriptional activation and repression properties, while GLI1 is a strong positive regulator of Hh transcriptional targets. In T-ALL rare hedgehog pathway mutations have been observed and approximately 20% of T-ALL cases present with ectopic expression of Hh pathway ligands and GLI1. However, the function of Hh signaling and in particular GLI transcription factors in T-ALL initiation and/or tumor progression is not well-known. RNA sequencing was performed in the CUTLL1 T-ALL cell line after knocking out GLI1 gene using CRISPR/Cas9 system. SOURCE: Erich Piovan (erich.piovan@unipd.it) - Universita’ di Padova
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