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Global transcriptome of bone marrow niche cells in homoestatis and human xenografts at late time points

ABSTRACT: We analysed the transcriptional signature in different niche cells extracted from the bone marrow of mice engrafted with human AML patient-derived samples or AML cell lines and compared it to the one of mice engrafted with human normal hematopoietic cells derived from cord blood or untransplanted mice

ORGANISM(S): Mus musculus

PROVIDER: GSE148624 | GEO | 2021/04/14

REPOSITORIES: GEO

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leukemia propagating cells rebuild an evolving niche in response to therapy

Project description:Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent vascular structures and endosteal linings in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a novel niche. We investigated patients’ BM biopsies and found evidence of a similar process in patients receiving induction-therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or niche-CPC interaction. We therefore identified a therapy-induced niche that protects CPCs. We used microarrays to compare the gene expression profile of ALL cell line (Nalm-6) from model (A0D) mice and rediduel cells from Ara-C treatment for 2 days (A2D) mice. Engrafted NALM-6-GFP+ cells from A0D mice and residual cells from A2D mice were flow sorted. Total RNA was isolated using RNeasy micro kit (Qiagen). Biotinylated cRNA was hybridized using HGU133Plus 2.0 GeneChip arrays (Affymetrix).

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leukemia propagating cells rebuild an evolving niche in response to therapy

2014-04-21 | GSE56273 | GEO

Global transcriptome of bone marrow niche cells in homoestatis and human xenografts at late time points

Project description:Global transcriptome of bone marrow niche cells in homoestatis and human xenografts at late time points

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Genome-wide effect of AML engraftment on bone marrow endothelial cells

Project description:We analysed the transcriptional signature in endothelial cells extracted from the bone marrow of mice engrafted with human AML and compared it to the one of mice engrafted with human normal hematopoietic cells

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Engraftment of limited numbers of pediatric leukemia into NOD/SCID/IL2Rcg-null mice enables surrogate markers for clinical outcome

Project description:Cultured immortalized cell lines have been extensively used to study the characteristics of various malignant stem cell clones and to optimize new treatment strategies. Nonetheless, the usefulness of such in vitro systems to recapitulate primary disease proved to be limited. Therefore, the design of more meaningful pre-clinical in vivo models ideally utilizing primary patient-derived material is of critical importance. In this context, the recently described NOD.Cg-Prkdcscid IL2rgtmWjl/Sz (NSG) mouse strain has been reported to sustain superior engraftment rates of patient-derived acute lymphatic and myeloid leukemic samples. However, limited data exist whether NSG-derived blasts retain their leukemogenecity over successive mouse generations and whether characteristics of this mouse model will indeed allow correlation to clinical parameters. In the present study, we thus engrafted NSG mice with 18 different pediatric B cell precursor ALL, AML and T-ALL samples and could demonstrate that NSG-derived blasts retained their leukemogenic profile with respect to immune-phenotype, chromosomal aberrations, transcriptome, flowcytometric- and PCR-minimal residual disease (MRD) marker expression. Moreover, the extent of leukemic engraftment and the overall survival of NSG mice highly correlated with the individual prognosis of pediatric B cell precursor ALL, AML and T-ALL patients. Thus, we here report on a complex in vivo model that provides a valuable tool for studying the heterogeneity of leukemic disease and for improving patient-tailored leukemia-targeting strategies . In the present study, we thus engrafted NSG mice with 18 different pediatric B cell precursor ALL, AML and T-ALL samples and could demonstrate that NSG-derived blasts retained their leukemogenic profile with respect to immune-phenotype, chromosomal aberrations, transcriptome, flowcytometric- and PCR-minimal residual disease (MRD) marker expression.

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