Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparative RNA sequencing identifies superior cytocidal mechanisms of imatinib over rapamycin in Pulmonary Lymphangioleiomyomatosis (LAM) Tumor Cells

ABSTRACT: We report results of RNA sequencing analysis of serum starved pulmonary LAM tumor cells comparatively treated for 24hrs at 37C and 5% CO2 with rapamycin (0.05uM and 1uM) and tyrosine kinase inhibitor (TKI) imatinib (1uM, 5uM, and 10uM). Experiments were done in duplicates per drug concentration. This study was performed to investigate the biological mechanisms underlying superior cytocidal capabilities of the TKI over FDA-approved rapamycin by inhibiting receptor tyrosine kinases on mesenchymal tumorigenic cells in Tuberous Sclerosis and Lymphangioleiomyomatosis (LAM) diseases. Total RNA isolates (RIN>8.0) were sequenced on an illumina Novaseq6000 platform at 100 base pairs to a depth of 20 milllion paired end reads. Real-Time Analysis was used for base callling converted to fastq format with bcl2fastq2. Pseudoalignment of RNA-seq reads to a kallisto index was created from human reference genome NCBI/GRCh38.p13. Differential expression was resolved using Sleuth in R and signaling pathway analysis was performed using Ingenuity Pathway Analysis (IPA). Results reveal differential inactivation of the Cell Cycle: G2/M DNA Damage Checkpoint Regulation SIgnaling Pathway only in pulmonary LAM tumor cells treated with 10uM imatinib concentration.We further determined that increasing imatinib conentrations from 1uM to 10uM induced endoplasmic reticulum inositol triphosphate receptor (IP3R) subtype switching from type I to type III typically associated with differential ER calcium efflux and apoptosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193398 | GEO | 2022/01/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Comparative RNA sequencing identifies superior cytocidal mechanisms of imatinib over rapamycin in UMB1949 renal angiomyolipoma cells

Project description:We report results of RNA sequencing analysis of serum starved UMB1949 renal angiomyolipoma (AML) cells comparatively treated for 24hrs at 37C and 5% CO2 with rapamycin (0.05uM and 1uM) and tyrosine kinase inhibitor (TKI) imatinib (1uM and 10uM). Experiments were done in triplicates per drug concentration. This study was performed to investigate the biological mechanisms underlying superior cytocidal capabilities of the TKI over FDA-approved rapamycin by inhibiting receptor tyrosine kinases on mesenchymal tumorigenic cells in Tuberous Sclerosis and Lymphangioleiomyomatosis (LAM) diseases. Total RNA isolates (RIN>8.0) were sequenced on an illumina Novaseq6000 platform at 100 base pairs to a depth of 30 milllion single end reads. Real-Time Analysis was used for base callling converted to fastq format with bcl2fastq2. Pseudoalignment of RNA-seq reads to a kallisto index was created from human reference genome NCBI/GRCh38.p13. Reads were also mapped to this reference genome using STAR (2.5.2b) and featureCounts (v1.5.0-p3) for results comparison. Differential expression was resolved using Sleuth and DESeq2 in R and signaling pathway analysis was performed using Ingenuity Pathway Analysis (IPA). Results reveal differential inactivation of the GPVI pathway and key cell survival and viability genes only in renal AML cells treated with imatinib conentrations.We further determined that this TKI differentially induced ER calcium efflux that disrupted mitochondrial permeability leading to increased cytosolic cytochrome C, caspase 3 activation and apoptosis.

2022-01-15 | GSE193402 | GEO

Inhibition of BCL6-dependent gene expression in Philadelphia chromosome positive acute lymphoblastic leukemia

Project description:The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. Tyrosine kinase inhibitors (TKI) are widely used to treat patients with leukemia driven by BCR-ABL1 and other oncogenic tyrosine kinases. In response to TKI-treatment, BCR-ABL1 ALL cells upregulate BCL6 protein levels by ~90-fold, i.e. to similar levels as in diffuse large B cell lymphoma (DLBCL) with BCL6 translocations. In this study, we analyzed the gene expression changes after treatment with Imatinib or Imatinib + RI-BPI. Three Ph+ ALL cell lines (BV-173, SUP-B15 and TOM-1) were treated in the presence or absence of 10 μM STI571 (Imatinib) or in the presence of both 10 μM STI571 and 20 μM RI-BPI for 24 hours.

2011-03-01 | E-GEOD-24381 | biostudies-arrayexpress

Inhibition of BCL6-dependent gene expression in Philadelphia chromosome positive acute lymphoblastic leukemia

2011-03-01 | GSE24381 | GEO

Exosomes released by imatinib-resistant K562 cells carry specific membrane markers and increase survival of imatinib-sensitive cells in the presence of imatinib.

Project description:Chronic myeloid leukemia is a malignant hematopoietic disorder distinguished by a presence of BCR-ABL fused oncogene with constitutive kinase activity. Although targeted therapy by tyrosine kinase inhibitors (TKI) markedly improved patient´s survival and quality of life, development of drug resistance remains a critical issue for a subset of patients. The most common mechanism of TKI resistance in CML patients is a mutation in BCR-ABL gene which makes oncogenic Bcr-Abl protein insensitive to TKI therapy. Mutation independent mechanisms of TKI resistance are less elucidated, but exosomes, extracellular vesicles excreted from normal and tumor cells were recently linked with cancer progression and drug resistance. We used an imatinib-sensitive CML cell line K562 and derived an imatinib-resistant subline K562IR by prolonged cultivation of cells in presence of imatinib. We demonstrated that exosomes isolated from K562IR cells are internalized by K562 cells and increase their survival in presence of 2µM imatinib. To characterize the exosomal cargo and to identify resistance-associated marker proteins, we performed a deep proteomic analysis of exosomes from both cell sublines using label free quantification (LFQ). In total, we identified over 3000 exosomal proteins including 31 proteins differentially abundant in exosomes derived from K562IR cells. Among the differential proteins were three massively upregulated membrane proteins in K562IR exosomes with surface localization: IFITM3, CD146, CD36. We verified the massive upregulation of the three proteins in K562IR exosomes and also in K562IR cells. Using flow cytometry, we further demonstrated potential of CD146 as cell surface marker associated with imatinib resistance in K562 cells.

2024-10-24 | PXD019283 | Pride

Whole-genome gene expression comparison of the chronic myeloid leukemia cell line K562 and its tyrosine kinase inhibitor resistant subclone K562-IR.

Project description:The aim of the analysis is to study the relationship between tyrosine kinase inhibitor (TKI) resistance mechanism and phenotypic plasticity in the TKI-resistant and parental chronic myeloid leukemia K562 cell lines, in the presence and absence of imatinib. Results provide insight into the molecular mechanisms underlying the acquisition of cancer cell plasticity.

2020-04-14 | GSE120932 | GEO

Recruitment of BCL6 to target genes in Philadelphia chromosome positive acute lymphoblastic leukemia

Project description:The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. Tyrosine kinase inhibitors (TKI) are widely used to treat patients with leukemia driven by BCR-ABL1 and other oncogenic tyrosine kinases. In response to TKI-treatment, BCR-ABL1 ALL cells upregulate BCL6 protein levels by ~90-fold, i.e. to similar levels as in diffuse large B cell lymphoma (DLBCL) with BCL6 translocations. In this study, we used genome tiling arrays to identify BCL6 target genes with specific recruitment of BCL6. Three Ph+ ALL cell lines (BV-173, NALM-1 and TOM-1) in duplicate were either treated with 10µM STI571 (Imatinib) for 24 hours or cultured in absence of STI571.

2011-02-15 | E-GEOD-24404 | biostudies-arrayexpress

Comparative RNA sequencing identifies superior cytocidal mechanisms of imatinib over rapamycin in Pulmonary Lymphangioleiomyomatosis (LAM) Tumor Cells

Project description:Comparative RNA sequencing identifies superior cytocidal mechanisms of imatinib over rapamycin in Pulmonary Lymphangioleiomyomatosis (LAM) Tumor Cells

| PRJNA796029 | ENA

Expression profiling in exosomal miRNAs of CML patients with musculoskeletal pain associated with discontinuation of Imatinib

Project description:An approximately 60% of chronic myeloid leukemia (CML) patients who achieved a deep molecular response for more than 2 years maintained a major molecular response after discontinuation of imatinib. These findings indicate the possibility that a portion of CML patients treated with Tyrosine kinase inhibitors (TKIs) could discontinue TKI therapy, although long-term prognosis and/or adverse events after TKIs cessation remain unclear. Recent reports showed that transient musculoskeletal pain occurs in approximately 30% of CML patients after stopping imatinib. To ascertain the factors underlying musculoskeletal events after TKI cessation, we investigated exosomal miRNA in five CML patients who did not experience musculoskeletal events and five patients with musculoskeletal pain after stopping TKIs.

2016-12-15 | GSE85903 | GEO

Integrative Single Cell Multiomic Profiling Analysis Reveals HOX-PBX Gene Regulatory Network Regulating the Survival of mTOR Hyperactive Cells [snRNA-Seq]

Project description:Lymphangioleiomyomatosis (LAM) is a rare, debilitating lung disease that predominantly affects women of reproductive age. LAM cells carry deleterious mutations of tuberous sclerosis complex (TSC1/TSC2) genes, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) and ultimately dysregulated cell growth. The integrative single cell omics data identified the activation of uterine specific HOX-PBX transcriptional programming in pulmonary LAMCORE cells. Network analysis predicted homeobox transcription factors including PBX1 and HOXD11 as key regulators controlling LAMCORE cell fate. Targeting the HOX-PBX network may have therapeutic value in LAM and TSC-related diseases, and possibly in other mTORC1-hyperactive neoplasms.

2023-04-03 | GSE217107 | GEO

Integrative Single Cell Multiomic Profiling Analysis Reveals HOX-PBX Gene Regulatory Network Regulating the Survival of mTOR Hyperactive Cells [snATAC-Seq]

2023-04-03 | GSE217106 | GEO