Expression data from OMP52M51 resistant or acute treated leukemic mice
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PROVIDER: PRJNA509685 | ENA |
REPOSITORIES: ENA
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Project description:We recently demonstrated that a human Notch1-specific neutralizing antibody (OMP52M51) was very effective in T-ALL patient derived xenografts (PDX) bearing NOTCH1/FBW7 mutations. However, we observed development of acquired resistance following long-term administration of the antibody and used PDX models to investigate this phenomenon. We analyzed expression profiles to identify genes and pathways modulated in mice treated until progression or acute treated with a neutralizing antibody against Notch1.
2020-05-20 | GSE123751 | GEO
Project description:Gene expression data of glucocorticoid resistant and sensitive acute lymphoblastic leukemia cell lines for the article: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC. Generation of the GC sensitive and resistant clones is described in Parson et al. FASEB J 2005 (Pubmed id 15637111). In brief GC sensitive clones were generated by limiting dilution subcloning from the GC sensitive T-ALL cell line CCRF-CEM-C7H2. To generate GC resistant clones the CCRF-CEM-C7H2 cell line was clutured in the presence of 10E-7 M dexametasone. Gene expression profiles of glucocorticoid (GC) resistant and sensitive T-ALL cells during GC treatment and corresponding control samples (cells treated with carrier control). GC induced regulation of PFKFB2 was determined in the various cell lines based on the expression intensities of the corresponding probe sets in GC treated and control samples.
2011-02-01 | E-GEOD-22152 | biostudies-arrayexpress
Project description:Gene expression data of glucocorticoid resistant and sensitive acute lymphoblastic leukemia cell lines for the article: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC. Generation of the GC sensitive and resistant clones is described in Parson et al. FASEB J 2005 (Pubmed id 15637111). In brief GC sensitive clones were generated by limiting dilution subcloning from the GC sensitive T-ALL cell line CCRF-CEM-C7H2. To generate GC resistant clones the CCRF-CEM-C7H2 cell line was clutured in the presence of 10E-7 M dexametasone.
2011-02-01 | GSE22152 | GEO
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2024-06-18 | E-MTAB-14003 | biostudies-arrayexpress
Project description:mRNA profiles of murine leukemic B cells (Eu-TCL1 mice) treated with extracellular vesicles were generated by 3'-sequencing, in triplicate.
2022-08-31 | GSE191186 | GEO
Project description:T-cell acute lymphoblastic leukemia is a hematological malignancy treated by chemotherapy, with a poor prognosis. We have demonstrated that activation of the T cell receptor (TCR) by anti-CD3 antibodies has a potent anti-leukemic effect in patient-derived xenograft models (PDX) of T-ALL. Therefore, with this experiment, we aim to identify the molecular mechanisms underlying the anti-leukemic properties of the OKT3 anti-CD3 mAb in T-ALL PDX.
2024-03-19 | GSE240296 | GEO
Project description:Drug-resistant acute myeloid leukemia
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Project description:YTHDF2 is overexpressed in a broad spectrum of human acute myeloid leukemias (AML). To study the role of YTHDF2 in leukemia, c-Kit+ cells from foetal livers of Ythdf2fl/fl;Vav-iCre (Ythdf2CKO) and Ythdf2fl/fl (Ythdf2CTL) 14.5 dpc embryos were transduced with Meis1 and Hoxa9 oncogenes and serially re-plated to generate pre-leukemic cells. Total RNA from Ythdf2CKO (n=5) and Ythdf2CTL (n=5) pre-leukemic cells were used for Affymetrix global gene expression analysis.
2019-04-05 | E-MTAB-6783 | biostudies-arrayexpress
Project description:Pre-leukemic stem cells (pre-LSCs) provide a reservoir of cells that evolve to acute leukemia and cause relapse following chemotherapy. We postulated that quiescence of pre-LSCs is an important mechanism of therapeutic resistance. Using a doxycycline-inducible H2B-GFP transgene in a mouse model of T-cell acute lymphoblastic leukemia, we show that long-term self-renewal, clonal evolution and resistance to chemo-radiation are intrinsically linked to restricted cell cycle. We show that restricted cell cycle of pre-LSCs requires the presence of the CDK inhibitor p21, with absence of p21 leading to chemosensitivity and clonal extinction by loss of asymmetric cell division and terminal differentiation. These results provide a model to identify and test strategies to eradicate an important source of clonal evolution and leukemic relapse.
2018-12-21 | GSE110132 | GEO