Signaling via NOTCH1 is reported to activate the PI3K pathway by inhibiting PTEN transcription (Palomero et al., 2007) and NOTCH1 was recently found to be mutated in CLL (Rosati et al., 2009; Fabbri et al., 2011; Balatti et al., 2012; Rossi et al., 2012) and is a predictor of survival (Rosati et al., 2009; Del Giudice et al., 2012; Rossi et al., 2012). The gene discussed is PIK3CD; the disease is B-cell chronic lymphocytic leukemia.