Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. We used gene expression profiling to analyze changes in the transcriptome of these leukemia cells over a 3-4 week period, taking samples at the start, the point at which most of the leukemia cells had been eradicated while a small percentage survived, and at the end when the cells were proliferating again.
Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.
Specimen part, Treatment, Time
View SamplesPrimary pre-B acute lymphoblastic (ALL) cells do not proliferate long-term ex vivo without the presence of stromal support. We developed and use an ex vivo co-culture model, consisting of mouse leukemic pre-B Bcr/Abl-expressing ALL cells grown with mitotically inactivated mouse embryonic fibroblasts (MEFs). This system provides a generic type of environmentally-mediated protection to the ALL cells, because when the ALL cells are treated with a moderate dose of a therapeutic drug, drug-resistant ALL cells can be recovered after a 1-2 week period of culture. Some of the factors produced by stromal cells that provide protection to ALL cells have been identified. However, it is unclear if the presence of drug-treated ALL cells affects the stromal fibroblasts. The current study was initiated to examine this using expression profiling on the irradiated MEFs.
Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.
Specimen part
View SamplesAffymetrix gene expression AID-GFP-positive vs AID-GFP-negative
The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia.
No sample metadata fields
View SamplesPrecursor B-lineage acute lymphoblastic leukemia (pre-B ALL) can be subdivided into different categories based on genetic abnormalities.
Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS function.
Specimen part
View SamplesThe Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. In this study, the tyrosine kinase inhibitor imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of Ph+ ALL cell lines were analyzed in response to imatinib treatment.
BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition.
Specimen part, Cell line
View SamplesThe Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which is present in almost every patient with chronic myeloid leukemia. In this study, the tyrosine kinase inhibitor Imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of CML cell lines were analyzed in response to Imatinib treatment.
BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition.
Specimen part, Cell line
View SamplesPrimary glioblastoma, representing over 90% of adult glioblastoma, develop rapidly without preexisting lower-grade glioma. We have generated a mouse model of primary glioblastoma driven by a single p53 mutation. These p53-mutant gliomas lose the syntenic region of human chromosome 10q, which is mapped to mouse chr19 and chr7. Loss of mouse chr19, containing Pten, activates PI3K/Akt signaling.
Murine models of IDH-wild-type glioblastoma exhibit spatial segregation of tumor initiation and manifestation during evolution.
No sample metadata fields
View SamplesTo examine molecular mechanisms of aortic valve stenosis in mice with hypertension and hypercholesterolemia, RNA-Seq was used during the developmental phase of stenosis to identify new gene targets. Overall design: Four groups of mice were studied: controls (CON), hypertensive (HT), hypercholesterolemic (HC), and HC/HT. Transgenic mice overexpressing human renin and human angiotensinogen served as the HT model and ApoE knockout mice served as the HC model. A sample size of N=4 was used for each of the four groups.
Fibrotic Aortic Valve Stenosis in Hypercholesterolemic/Hypertensive Mice.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Specimen part
View SamplesIn gastrulation, distinct progenitor cell populations are induced and sorted into the three germ layers ectoderm, mesoderm and endoderm. In order to identify genes involved in germ layer specification and morphogenesis, we identified genes differentially expressed between ectodermal and mesendodermal progenitor cells. To do so, we first generated highly enriched pools of ectodermal and mesendodermal progenitor cells. Mesendodermal cells were generated by over-expressing the Nodal signal Cyclops in wild type embryos and ectodermal cells were taken from mz-one-eyed-pinhead (oep) mutant embryos. We then compared the transcriptome of ectodermal versus mesendodermal cells taken from embryos at 7 hours post fertilization (hpf). In wild type embryos at this stage (70% epiboly), the first ectodermal and mesendodermal progenitor cells have already been sorted into their respective germ layers and ingression of mesendodermal progenitors is still ongoing.
Identification of regulators of germ layer morphogenesis using proteomics in zebrafish.
Age, Specimen part, Subject, Time
View Samples