Chronic Lymphocytic Leukemia (CLL): A Comparative Analysis of Protein Expression Profiles in Peripheral Blood Cells at Diagnosis and upon Disease Progression.
Authors: Gine Eva , Muntañola Ana , Crespo Marta , Calpe Eva , Gomes Maria Joao , Montserrat Emili , Bosch Francesc 
Published: October 2019

CLL has a heterogeneous clinical course. Although some genetic abnormalities such as del(17p) have been associated with disease progression, the mechanisms underlying such a phenomenon are not well-known. The aim of the present study was to compare protein expression profiles in CLL cells at diagnosis and upon disease progression in patients with early, low-risk CLL. We studied 6 patients in early stage and without poor risk cytogenetics (i.e., +12, 11q-, 17p-) for which leukemic cells at diagnosis and at disease progression were available. Patients with low-risk disease progressing or receiving therapy within the first 2 years after diagnosis were not eligible for the study. Cell purity of samples at diagnosis and at progression was high(mean CD5+/CD19+ cells 90% and 91%, respectively). Protein expression profile was analyzed by using a Fluorescence 2-D Difference Gel Electrophoresis (DIGE). Image analysis and statistical quantification of relative protein levels were performed using DeCyder V. 5.0 software (GE Healthcare) and the identification of differential spots by MALDI-MS analysis. Different protein expression patterns between diagnosis and disease progression samples were onserved both in the whole group of patients (table 1) and in paired samples. Proteins undergoing significant changes in their expression levels are involved in the ubiquitin-dependent degradation pathway, carbohydrate metabolism, and RNA cytoplasmic transport. In addition several of the proteins identified, such as EF-2, HNR, annexin A1 and nucleophosmine, have a role in cell proliferation and human oncogenesis. In conclusion this study identified changes on the expression of a number of proteins that are part of important oncogenic pathways in CLL progression.

Identification of differential spots Identification (p value &lt; 0.05/1.2 fold) Ratio (Pr/Dx) Pr: Progression; Dx: Diagnosis Protein Catabolism Ubiquitin thiolesterase −1.59 Ubiquitin-protein ligase E1 −1.42 Elongation factor 2 (EF-2) −1.39 Acyaminoacyl-peptidase −1.25 Protein disulfide-isomerase precursor −1.21 Carbohydrate Catabolism Glucose-6-phosphate 1-dehydrogenase −1.31 Fructose -bisphosphate aldolase A −1.25 Phosphoglycerate kinase 1 −1.21 RNA Processing Heterogeneous nuclear ribonucleoprotein C 1.49 Heterogeneous nuclear ribonucleoprotein A3 1.30 Heterogeneous ribonuclear particle protein A1. Beta 1.27 Pre-mRNA cleavage factor I 25 kDa subunit 1.25 Cytoskeleton ACTB −1.67 Actinin alpha 4 −2.03 CAP1 −1.31 Cytoplasmatic dynein intermediate chain 2 −1.35 L-Plastin −1.42 Tropomyosin alpha 4 chain −1.38 Vinculin −2.48 Others Annexin A1 −1.6 Glycine-tRNA ligase (EC 6.1.1.14) precursor −1.34 HSU12596 −1.53 IQGAP1 protein −1.51 Peroxiredoxin 3 1.28 probable transitional endoplasmic reticulum ATPase −1.52 Nucleophosmin 1.25 Proteinase inhibitor 9 −1.34 purH bifunctional enzyme −1.32 tryptophan-tRNA ligase −1.31 WDR1 protein −1.51 Zeta-crystallin/quinine reductase (NADPH) 1.25