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- W2017018947 abstract "The presence of MRD/NTICs in autologous HPBSC collections and the high frequency of disease recurrence have great concerns for transplantation. Several studies have shown that the infusion of tumor cells with the HPBSC graft is strongly associated with relapse. In this study we confirm the presence of MRD/NTICs in HPBSC collected from patients who underwent autologous transplantation. Eighteen samples from HPBSC collected from children diagnosed with high-risk neuroblastoma by apheresis (COBE spectra) were deemed to be suitable for transplantation (lack expression of Tyrosine Hydroxylase (TH) and ICC negative). At the time of collection, patients were assessed to be in clinical remission (CR) or very good partial remission (VGPR). An aliquot from each collection was assessed by various methods: gene expression of TH and MYCN by qRT-PCR, surface marker immunophenotype using CD56 (NCAM), GD2 and CD9 by flow cytometry and placed on LTC-IC, after CD133 positive selection, viability and clonogenicity of cells as well as gene expression (TH, MYCN) were assessed at 8 weeks in culture. Undetectable gene expression (TH or MYCN) was observed on day 0 compared to 1.8 x0 and 1.4 x-1 in negative controls vs. 2.9x6 and 9.0x2 for human neuroblastoma cell lines. At week 8 in LTCIC there was 6.5x3 fold increased in expression of TH and 1.6x3 fold increased in MYCN gene expression in patient samples. while negative controls showed no increase of gene expression and no change in gene expression in the neuroblastoma cell lines. The patient samples also formed spheres, both adherent and non-adherent that were similar morphologically and by immunofluorescence to neurospheres generated from neural stem cells. Generation of self-renewing cells post CD 133 selection show extensive cell proliferation with limited differentiation on patient samples consistent with characteristic to TICs. In contrast, negative controls progressed into quiescence or apoptosis. We conclude that HPBSC who were assessed as free of tumor at the time of collection show the presence of MRD/TIC detected at week 8 in LTCIC. Further studies to determine if these cells have the ability to initiate tumors need to be performed." @default.
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- W2017018947 date "2012-02-01" @default.
- W2017018947 modified "2023-09-27" @default.
- W2017018947 title "Minimal Residual Disease (MRD) and Neuroblastoma Tumor Initiating Cells (NTICs) in Hematopoietic Peripheral Stem Cell (HPBSC) Collections from High Risk Neuroblastoma Children Was Assessed by Gene Expression of TH,MYCN Using Quantitative Real Time PCR (qRT-PCR), Immunophenotype Analysis and Long Term Culture Initiating Cell (LTC-IC)" @default.
- W2017018947 doi "https://doi.org/10.1016/j.bbmt.2011.12.272" @default.
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