Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

Figure 2

Ca²⁺-dependent signaling pathways in T-ALL. Ca²⁺ influx may occur through CRAC channels, activated in receptor-dependent manner: (a) muscarinic receptors (M1–M5) are stimulated by Ach produced by leukemic cells themselves, but mechanisms of elevated Ach production are not studied yet; (b) TCR or preTCR receptors are activated through mechanisms which may engage Notch upregulation. Another mechanism for Ca²⁺ influx involves activation of nonselective Ca²⁺-permeable channels, activated by different mechanisms. Driving force for sustained Ca²⁺ influx is generated by K⁺ efflux through selective K⁺ channels. Most important genetic lesions and signaling pathways are indicated, together with percentages for each type of lesion recognized in clinical cases. For more details, see the text.