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Series GSE176141 Query DataSets for GSE176141
Status Public on Jun 05, 2021
Title Identification of altered cell signaling pathways in stable and progressive chronic lymphocytic leukemia
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Chronic lymphocytic leukemia (CLL) is characterized by significant biological and clinical heterogeneity. This study was designed to explore CLL B-cells’ proteomic profile in order to identify biological processes affected at an early stage and during disease evolution as stable or progressive. Purified B cells from 11 untreated CLL patients were tested at two time points by liquid chromatography-tandem mass spectrometry. Patients included in the study evolved to either progressive (n=6) or stable disease (n=5). First, at an early stage of the disease (Binet stage A), based on the relative abundance levels of 389 differentially expressed proteins (DEP), samples were separated into stable and progressive clusters with the main differentiating factor being RNA splicing pathway. Next, in order to test how the DEPs affect RNA splicing, a RNA-Seq study was conducted for 4 Stable and 4 Progressive CLL patients, showing 4217 differentially spliced genes between the two clusters. Distinct longitudinal evolutions were observed with predominantly proteomic modifications in the stable CLL group and spliced genes in the progressive CLL group. Splicing events were shown to be 6 times more frequent in the progressive CLL group. The main aberrant biological processes controlled by DEP and spliced genes in the progressive group were cytoskeletal organization, Wnt/β-catenin signaling, mitochondrial and inositol phosphate metabolism with a downstream impact on CLL B-cell survival and migration. This study suggests that proteomic profiles at the early stage of CLL can discriminate progressive from stable disease and that RNA splicing dysregulation underlies CLL evolution, which opens new perspectives in terms of biomarkers and therapy.
Overall design Purified B cells from 8 untreated CLL patients were tested at two time points by RNA-Seq. Patients included in the study evolved to either progressive (n=4, samples tested at diagnosis in Binet A disease and at the time of progressive disease to Binet B/C) or stable disease for more than 5 years (n=4, samples tested at diagnosis and 3 years after diagnosis).
Longitudinal study of stable and progressive CLL.
Contributor(s) Bagacean C, Renaudineau Y
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Submission date Jun 04, 2021
Last update date Jun 07, 2021
Contact name Cristina Bagacean
Phone 0604148674
Organization name UBO
Street address 2 Avenue Foch
City Brest
ZIP/Postal code 29200
Country France
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (16)
GSM5356880 Progressive1 T0
GSM5356881 Progressive1 T1
GSM5356882 Progressive2 T0
BioProject PRJNA735097
SRA SRP322666

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE176141_FPKM_Gencode.xlsx 4.8 Mb (ftp)(http) XLSX
GSE176141_RAW.tar 10.3 Gb (http)(custom) TAR (of BW)
GSE176141_SummaryDifferentialExonUsage_Progressive_T0_vs_Stable_T0.xlsx 602.4 Kb (ftp)(http) XLSX
GSE176141_SummaryDifferentialExonUsage_Progressive_T1_vs_Progressive_T0.xlsx 25.1 Kb (ftp)(http) XLSX
GSE176141_SummaryDifferentialExonUsage_Stable_T1_vs_Stable_T0.xlsx 12.4 Kb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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