Given the mutational profiles and constitutive kinase signaling in both Ph-like ALL and DS-ALL, we hypothesized in the current study that co-targeting of (1) the extracellular highly-expressed cell surface TSLPR with CAR T cell immunotherapy and (2) intracellular JAK/STAT signaling with ruxolitinib could have synergistic anti-leukemia activity in CRLF2+ Ph-like and DS-ALL. This evidence concerns the gene CRLF2 and acute lymphoblastic leukemia.