Proteomics-based identification of cancer-associated proteins in chronic lymphocytic leukaemia

Background Chronic lymphocytic leukaemia (CLL) is a neoplasm of B-cells characterized by variable prognosis. Exploring the proteome of CLL cells may provide insights into the disease. Therefore, eleven proteomics experiments were conducted on eleven primary CLL samples. Results We reported a CLL proteome consisting of 919 proteins (false discovery rate (FDR) ≤ 1%) whose identification was based on the sequencing of two or more distinct peptides (FDR of peptide sequencing ≤ 1%). Mass spectrometry-based protein identification was validated for four different proteins using Western blotting and specific antibodies in different CLL samples. Small sizes of nucleolin (~57 kDa and ~68 kDa) showed a potential association with good prognosis CLL cells (n = 8, p < 0.01). Compared with normal B-cells, CLL cells over-expressed thyroid hormone receptor-associated protein 3 (THRAP3; n = 9; p = 0.00007), which is implicated in cell proliferation; and heterochromatin protein 1-binding protein 3 (HP1BP3; n = 10; p = 0.0002), which promotes cell survival and tumourogenesis. A smaller form of HP1BP3, which may correspond to HP1BP3 isoform-2, was specifically identified in normal B-cells (n = 10; p = 0.0001). HP1BP3 and THRAP3 predicted poor prognosis of CLL (p ≤ 0.05). Consistently, THRAP3 and HP1BP3 were found to be associated with cancer-related pathways (p ≤ 0.05). Conclusions Our findings add to the known proteome of CLL and confirm the prognostic importance of two novel cancer-associated proteins in this disease