Rapamycin derivatives inhibit AKT signaling in leukemic cells in vivo. (A) Peripheral blood mononuclear cells from patients treated with either everolimus or temsirolimus were subjected to immunoblotting analyses of pAKT, total AKT, and GAPDH, and (B) quantitative real-time PCR analysis of CCND1/CCND2 and GLUT1 transcription. The data shown are derived from TaqMan PCR analyses of these genes. (C) Changes in white blood cell count (WBC, 109/L) and absolute blast count (ABC, 109/L) during temsirolimus treatment. (i) Patient with relapsed refractory pre-B-cell acute lymphoblastic leukemia (pre-B-ALL) received 3 doses of temsirolimus at a dose of 25 mg intravenously every week (indicated by arrows). (ii) Patient with primary refractory AML has completed 2 courses of temsirolimus (4 weekly injections each, at a dose of 25 mg intravenously every week) and received 2 doses of temsirolimus in course 3.
