Genomic imbalances affecting TGF-β and PI3K-AKT signaling pathways. Gain of SMURF1 and deletion of TCRG (A), deletion of CBLB (B), gains of IGF2 (C) as well as MSI2 (D). Aberrations are indicated by arrows. All data points are shown as log2-ratios comparing T-ALL DNA with a pool of normal blood DNA from 10 donors. Clones are plotted in chromosome order. Effectors and inhibitors of TGF-β (E) and PI3K-AKT (F) signaling targeted by DNA copy-number changes are marked in green (gains) and red (deletions). SMURF1, Smad ubiquitination regulatory factor 1; SMURF2, SMAD-specific E3 ubiquitin protein ligase 2; SMAD, mothers against DPP homolog; P300, E1A binding protein p300; CDKN1A, cyclin-dependent kinase inhibitor 1A; CDKN1B, cyclin-dependent kinase inhibitor 1B; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; IRS1-4, IRS; PTEN, phosphatase and tensin homolog deleted on chromosome 10; PDK1, phosphoinositide-dependent kinase 1; PKB, protein kinase B also named AKT; FOXO3A, forkhead box O3A; BIM, BCL2-like 11 (apoptosis facilitator); MAPK, MAP kinases; MEK, MAP kinase-mitogen activated protein kinase; ERK, MAP kinases Erk1 and 2; MKNK2, MAP kinase interacting serine/threonine kinase 2; MSI2, musashi homolog 2; RAS, RAF kinases; c-myc, oncogene; PRKCA, protein kinase Cα.
