The Sheba group has been the co-discoverer of a subgroup of high risk acute lymphoblastic leukemias (ALL) characterized by aberrant expression of the receptor CRLF2 and activating mutations in CRLF21IL7R1JAK proteins. These CRLF2-ALLs are associated with poor outcome and no effective treatments.  The team will test the effect of inhibitors on CRLF2-ALL cell lines and patient derived xenografts in-vitro and in-vivo to evaluate their effect on anti-tumor immune activation. City of Hope is currently moving forward to clinically test CpG-STAT3siRNA in patients with B cell lymphoma as well as malignant glioma.  Positive findings from theses proposed studies have the potential to create effective new therapies to benefit ALL patients who fail current treatment.