344P B cell precursor acute lymphoblastic leukemia (ALL) shows similar drug response in pdx mice and the corresponding patient

Abstract

Background Cumulative toxicities and drug resistance limit chemotherapy treatment after the first-line regimen. Tumors from patient-derived xenograft (PDX) models closely recapitulate the tumors from the same patient, regarding to their histopathological and genetic profiles. However, it is still unknown whether drug response of B-ALL in PDX mice can reflect the patient clinic outcome. In this study, pre-B ALL PDX model were established and examined to determine responses of the established leukemia to two conventional chemotherapeutic regimens. Using the PDX mice model, we compared the drug response in PDX mice with the clinic outcome of the corresponding patient. Methods PDX models were established by being injected with pre-B ALL samples from eight patients into NOD-SCID-IL2RG-/- (NSI) mice. The PDX models of each patient were then divided into three groups that were treated with VDLP regimen (vincristine+daunorubicin+l-asparaginasum+prednisone), HYPER-CVAD regimen (Methotrexate+cytarabine+cyclophosphamide+vincristine+Adriamycin+xamethasone), and PBS respectively. In parallel, eight patients were treated with VDLP regimen. Clinical outcomes of treated patients were collected. Results Xenografts of pre-B ALL presented with major biological characteristics of the original cancers. 0rv5% pre-B ALL cells in blood marrow of PDX mice is defined as complete remission; pre-B ALL cells 2:20% is defined as no remission. Six out of eight patients achieved complete remission after being treated with VDLP regimen. Consistently, B-ALL cells were completely eliminated after treatment of VDLP and HYPER-CVAD regimens in the PDX mice of these six patients. Two patients failed to achieve remission after VDLP treatment, whose B-ALL cells were also resistant to both VDLP and HYPER-CVAD regiments in xenografts. Conclusions Our results demonstrate that drug efficacy assessments based on PDX mice were consistent to clinical outcomes of the patient. PDX mice may potentially serve as a tool to optimize the clinic treatment for individual therapy. Legal entity responsible for the study Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Funding Hichuang Biomedical(Chongqing)Corp. Disclosure All authors have declared no conflicts of interest.