Preclinical evaluation of a novel treatment strategy to treat high risk ALL

We recently showed that rapid engraftment of patient ALL in NOD/SCID mice is indicative for poor patient survival. Moreover, gene expression analysis identified differenzial expression of molecules regulating the mTOR pathway. We now functionally address mTOR activation assessing P-S6 levels in xenograft ALL and evaluate mTOR inhibition as novel treatment strategy ex vivo and in vivo. Increased P-S6 levels were detected in TTLshort compared to TTLlong xenografts indicating constitutive mTOR hyperactivation in TTLshort/early relapse leukemia. Furthermore, the mTOR inhibitors rapamycin and BEZ235 significantly dec…