LEF1 gene alterations and their biological and clinical impact. (A) LEF1 gene alterations are found in 13% of the T-ALL cases, of which 14.3% are point mutations, 28.6% large deletions, and 57.1% focal deletions. Patients with LEF1 gene alterations display a higher prevalence of central nervous system involvement. (B) Focal deletions lead to a short isoform lacking exons 2 and 3 (LEF1 del2/3). Contrary to WT LEF1 (LEF1 WT), this isoform acts in a dominant-negative manner, inhibiting Wnt signaling. LEF1 del2/3 T-ALL cells are more susceptible to calcineurin inhibition and glucocorticoids than LEF1 WT T-ALL cells. CNS, central nervous system; WT, wild type. Illustration by A. Rita Fragoso and Marta B. Fernandes.

LEF1 gene alterations and their biological and clinical impact. (A) LEF1 gene alterations are found in 13% of the T-ALL cases, of which 14.3% are point mutations, 28.6% large deletions, and 57.1% focal deletions. Patients with LEF1 gene alterations display a higher prevalence of central nervous system involvement. (B) Focal deletions lead to a short isoform lacking exons 2 and 3 (LEF1 del2/3). Contrary to WT LEF1 (LEF1 WT), this isoform acts in a dominant-negative manner, inhibiting Wnt signaling. LEF1 del2/3 T-ALL cells are more susceptible to calcineurin inhibition and glucocorticoids than LEF1 WT T-ALL cells. CNS, central nervous system; WT, wild type. Illustration by A. Rita Fragoso and Marta B. Fernandes.

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