Simultaneous inhibition of IGF-1R with drug altering AMPK, mTOR, or Akt signaling pathway induces synergistic growth inhibition in ALL cell lines. Cell growth of ALL CCRF-CEM and NALM6 cells treated with either AICAR (100 μM) plus the IGF-1R inhibitor HNMPA(AM)3 (1.0 μM) (panel A); AICAR (200 μM) plus the Akt inhibitor-X (AIX, 9.0 μM) (panel B); or rapamycin (1.0 μg/ml) plus HNMPA(AM)3 (0.5 and 1.0 μM) (panel C). Cells were treated with either agent alone or in combination at the indicated doses and incubated for 24 h at 37°C. The cell growth values are expressed as a percentage relative to those obtained with control cells (mean ± SEM, n = 3). Combination index (CI) values were determined for each drug combination as described in Methods (CI <1 indicates synergism).