Comprehensive characterization of patient-derived xenograft models of pediatric leukemia.

Autor: Rogojina A; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA., Klesse LJ; Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Gill Center for Cancer and Blood Disorders, Children's Health Children's Medical Center, Dallas, TX, USA., Butler E; Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Gill Center for Cancer and Blood Disorders, Children's Health Children's Medical Center, Dallas, TX, USA., Kim J; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA., Zhang H; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA., Xiao X; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA., Guo L; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA., Zhou Q; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA., Hartshorne T; Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Garcia D; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA., Weldon K; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA., Holland T; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA., Bandyopadhyay A; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA., Prado LP; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA., Wang S; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA., Yang DM; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA., Langevan AM; Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA., Zou Y; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA., Grimes AC; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA.; Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA., Assanasen C; Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA., Gidvani-Diaz V; Methodist Children's Hospital, San Antonio, TX, USA., Zheng S; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA.; Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, TX, USA., Lai Z; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA.; Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX, USA., Chen Y; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA.; Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, TX, USA., Xie Y; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Tomlinson GE; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA.; Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA., Skapek SX; Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Gill Center for Cancer and Blood Disorders, Children's Health Children's Medical Center, Dallas, TX, USA., Kurmasheva RT; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA., Houghton PJ; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA.; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA., Xu L; Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Quantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jazyk: angličtina
Zdroj: IScience [iScience] 2023 Oct 10; Vol. 26 (11), pp. 108171. Date of Electronic Publication: 2023 Oct 10 (Print Publication: 2023).
DOI: 10.1016/j.isci.2023.108171
Abstrakt: Patient-derived xenografts (PDX) remain valuable models for understanding the biology and for developing novel therapeutics. To expand current PDX models of childhood leukemia, we have developed new PDX models from Hispanic patients, a subgroup with a poorer overall outcome. Of 117 primary leukemia samples obtained, successful engraftment and serial passage in mice were achieved in 82 samples (70%). Hispanic patient samples engrafted at a rate (51/73, 70%) that was similar to non-Hispanic patient samples (31/45, 70%). With a new algorithm to remove mouse contamination in multi-omics datasets including methylation data, we found PDX models faithfully reflected somatic mutations, copy-number alterations, RNA expression, gene fusions, whole-genome methylation patterns, and immunophenotypes found in primary tumor (PT) samples in the first 50 reported here. This cohort of characterized PDX childhood leukemias represents a valuable resource in that germline DNA sequencing has allowed the unambiguous determination of somatic mutations in both PT and PDX.
Competing Interests: The authors declare no conflicts of interest.
(© 2023 The Authors.)
Databáze: MEDLINE