1 research outputs found
Proteomics-Based Strategies To Identify Proteins Relevant to Chronic Lymphocytic Leukemia
Chronic
lymphocytic leukemia (CLL), a malignant B-cell disorder,
is characterized by a heterogeneous clinical course. Two-dimensional
nano liquid chromatography (2D-nano–LC) coupled with matrix-assisted
laser desorption/ionization time-of-flight tandem mass spectrometry
(MALDI-TOF/TOF MS) (LC–MALDI) was used to perform qualitative
and quantitative analysis on cellular extracts from 12 primary CLL
samples. We identified 728 proteins and quantified 655 proteins using
isobaric tag-labeled extracts. Four strategies were used to identify
disease-related proteins. First, we integrated our CLL proteome with
published gene expression data of normal B-cells and CLL cells to
highlight proteins with preferential expression in the transcriptome
of CLL. Second, as CLL’s outcome is heterogeneous, our quantitative
proteomic data were used to indicate heterogeneously expressed proteins.
Third, we used the quantitative data to identify proteins with differential
abundance in poor prognosis CLL samples. Fourth, hierarchical cluster
analysis was applied to identify hidden patterns of protein expression.
These strategies identified 63 proteins, and 4 were investigated in
a CLL cohort (39 patients). Thyroid hormone receptor-associated protein
3, T-cell leukemia/lymphoma protein 1A, and S100A8 were associated
with high-risk CLL. Myosin-9 exhibited reduced expression in CLL samples
from high-risk patients. This study shows the usefulness of proteomic
approaches, combined with transcriptomics, to identify disease-related
proteins