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Multipronged functional proteomics approaches for global identification of altered cell signalling pathways in B‐cell chronic lymphocytic leukaemia
Author(s) -
Díez Paula,
Lorenzo Seila,
Dégano Rosa Mª,
Ibarrola Nieves,
GonzálezGonzález María,
Nieto Wendy,
Almeida Julia,
González Marcos,
Orfao Alberto,
Fuentes Manuel
Publication year - 2016
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201500372
Subject(s) - proteomics , biology , chronic lymphocytic leukemia , transcriptome , antibody microarray , microarray , signal transduction , b cell , antibody , cancer research , computational biology , genetics , gene , gene expression , leukemia
Chronic lymphocytic leukaemia (CLL) is a malignant B cell disorder characterized by its high heterogeneity. Although genomic alterations have been broadly reported, protein studies are still in their early stages. Herein, a 224‐antibody microarray has been employed to study the intracellular signalling pathways in a cohort of 14 newly diagnosed B‐CLL patients as a preliminary study for further investigations. Several protein profiles were differentially identified across the cytogenetic and molecular alterations presented in the samples (deletion 13q14 and 17p13.1, trisomy 12, and NOTCH1 mutations) by a combination of affinity and MS/MS proteomics approaches. Among others altered cell signalling pathways, PKC family members were identified as down‐regulated in nearly 75% of the samples tested with the antibody arrays. This might explain the rapid progression of the disease when showing p53, Rb1, or NOTCH1 mutations due to PKC‐proteins family plays a critical role favouring the slowly progressive indolent behaviour of CLL. Additionally, the antibody microarray results were validated by a LC‐MS/MS quantification strategy and compared to a transcriptomic CLL database. In summary, this research displays the usefulness of proteomic strategies to globally evaluate the protein alterations in CLL cells and select the possible biomarkers to be further studied with larger sample sizes.