Dataset Information

Cell line xenograft experiment

ABSTRACT: Pediatric ALL cell line 380 was injected via tail vein into NSG mice. Triplicate 380 cell samples were also prepared at the timepoint of injection and stored at -80 oC for comparative analysis with CDXs. Mice were euthanized at onset of leukemia symptoms and spleen, bone marrow and liver samples were collected for proteomics analysis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr. Philipp Lange

PROVIDER: MSV000086727 | MassIVE | Wed Jan 20 02:20:00 GMT 2021

SECONDARY ACCESSION(S): PXD023697

REPOSITORIES: MassIVE

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Publications

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways.

Uzozie Anuli C AC Ergin Enes K EK Rolf Nina N Tsui Janice J Lorentzian Amanda A Weng Samuel S H SSH Nierves Lorenz L Smith Theodore G TG Lim C James CJ Maxwell Christopher A CA Reid Gregor S D GSD Lange Philipp F PF

Journal of experimental & clinical cancer research : CR 20210315 1

<h4>Background</h4>Murine xenografts of pediatric leukemia accurately recapitulate genomic aberrations. How this translates to the functional capacity of cells remains unclear. Here, we studied global protein abundance, phosphorylation, and protein maturation by proteolytic processing in 11 pediatric B- and T- cell ALL patients and 19 corresponding xenografts.<h4>Methods</h4>Xenograft models were generated for each pediatric patient leukemia. Mass spectrometry-based methods were used to investig ...[more]

PMID: 33722259

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Project description:Glucocorticoids are critical components of combination chemotherapy regimens in pediatric acute lymphoblastic leukemia (ALL). The pro-apoptotic BIM protein is an important mediator of glucocorticoid-induced apoptosis in normal and malignant lymphocytes, while the anti-apoptotic BCL2 confers resistance. The signaling pathways regulating BIM and BCL2 expression in glucocorticoid-treated lymphoid cells remain unclear. In this study, pediatric ALL patient-derived xenografts (PDXs) inherently sensitive or resistant to glucocorticoids were exposed to dexamethasone in vivo. In order to understand the basis for differential in vivo glucocorticoid sensitivity of PDXs, microarray analysis of gene expression was carried out on 5 each of dexamethasone-sensitive and resistant PDXs . This provided a global understanding of dexamethasone-induced signaling cascades in ALL cells in vivo, and especialy identified the genes that are involved in transducing the apoptotic signal, upstream of BIM/BCL2 dynamic interactions. ALL xenograft cells were inoculated by tail-vein injection into NOD/SCID mice, and engraftment was monitored weekly. When >70% %huCD45+ engraftment in the peripheral blood was apparent, which occurred 8-10 weeks post-transplantation, mice were treated with either dexamethasone (15 mg/kg) or vehicle control by intra-peritoneal (IP) injection, and culled at 8 hours following the treatment. Cell suspensions of spleens were prepared and mononuclear cells enriched to >97% human by density gradient centrifugation. RNA was extracted using the RNeasy Mini Kit (QIAGEN, Valencia, CA, USA), and RNA samples with integrity number (RIN) > 8.0 were amplified and hybridized onto Illumina HumanWG-6 v3 Expression BeadChips (6 samples/chip). All chips (with associated reagents) were purchased from Illumina, and scanned on the Illumina BeadArray Reader according to the manufacturer’s instructions. Microarray data were analyzed using the online modules in GenePattern. 10 xenografts were derived from patients of 5 dexamethasone-good responder and 5 dexamethasone-poor responder. Each xenograft was innoculated into 5-6 mice, and treated with dexamethasone (15 mg/kg) or vehicle control. In total spleen-harvest xenograft samples from 58 mice were analyzed using microarray.

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Dataset Information

Cell line xenograft experiment

Publications

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways.

Similar Datasets

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