In summary, we demonstrate robust curative potential of TSLPRCART immunotherapy in preclinical models of human CRLF2-rearranged Ph-like ALL and DS-ALL and an optimized time-sequenced JAK inhibitor co-therapy strategy that both mitigates acute CRS-like toxicity and potential CAR T cell exhaustion and maximizes long-term leukemia remission durability. This evidence concerns the gene CRLF2 and acute lymphoblastic leukemia.