Tumor homografts are transplants of GEMM tumors into immunocompetent syngeneic hosts. Our acute lymphoblastic leukemia tumor homografts feature NRAS activating mutations, which are associated with early relapse and chemoresistance in the clinic, as well as clinically-relevant fusion genes. Our tumor homografts preserve these original GEMM tumor driver mutations and provide robust and synchronous growth suited for in vivo pharmacology studies.