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Identification of altered cell signaling pathways using proteomic profiling in stable and progressive chronic lymphocytic leukemia
- Source :
- Journal of Leukocyte Biology, Journal of Leukocyte Biology, 2022, 111 (2), pp.313-325. ⟨10.1002/JLB.4HI0620-392R⟩
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
Abstract
- Chronic lymphocytic leukemia (CLL) is characterized by significant biologic and clinical heterogeneity. This study was designed to explore CLL B-cells’ proteomic profile in order to identify biologic 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 (DEPs), samples were separated into stable and progressive clusters with the main differentiating factor being the RNA splicing pathway. Next, in order to test how the DEPs affect RNA splicing, a RNA-Seq study was conducted 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 six times more frequent in the progressive CLL group. The main aberrant biologic processes controlled by DEPs and spliced genes in the progressive group were cytoskeletal organization, Wnt/β-catenin signaling, and 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.
- Subjects :
- Male
MESH: Leukemia, Lymphocytic, Chronic, B-Cell / genetics
Proteome
[SDV]Life Sciences [q-bio]
Chronic lymphocytic leukemia
Disease
Stable Disease
hemic and lymphatic diseases
Immunology and Allergy
Longitudinal Studies
RNA-Seq
liquid chromatography-tandem mass spectrometry
MESH: Leukemia, Lymphocytic, Chronic, B-Cell / pathology
MESH: Longitudinal Studies
Wnt Signaling Pathway
B-Lymphocytes
MESH: Middle Aged
Wnt signaling pathway
MESH: Follow-Up Studies
MESH: Gene Expression Regulation, Neoplastic
Middle Aged
Cell cycle
Prognosis
Gene Expression Regulation, Neoplastic
[SDV] Life Sciences [q-bio]
MESH: B-Lymphocytes / metabolism
RNA splicing
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
cell cycle
[SDV.IMM] Life Sciences [q-bio]/Immunology
RNA Splicing
Immunology
[SDV.CAN]Life Sciences [q-bio]/Cancer
splicing
Biology
MESH: Prognosis
MESH: Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
MESH: Biomarkers, Tumor / genetics
[SDV.CAN] Life Sciences [q-bio]/Cancer
Biomarkers, Tumor
medicine
Humans
Aged
Retrospective Studies
Proteomic Profile
Proteomic Profiling
Cell Biology
MESH: B-Lymphocytes / pathology
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
MESH: Male
Cancer research
chronic lymphocytic leukemia
MESH: Female
Follow-Up Studies
Subjects
Details
- ISSN :
- 19383673 and 07415400
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- Journal of Leukocyte Biology
- Accession number :
- edsair.doi.dedup.....89c0e8a083104e71222aa68c222ad12b