Quantitative proteomic analysis of CLL B-cells from mutated and unmutated IgVH subgroups using a label-free approach: Poster ID: 350

Introduction: Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease and subsequently, there is a need for prognostic markers to predict disease course and treatment initiation. Currently used prognostic indicators include clinical markers, cell based markers, the presence of soluble factors in the serum and genetic markers. Amongst these, the mutational status of the immunoglobulin variable heavy chain (IgVH) remains one of the most important and predicative biomarkers.

There is a strong correlation between IgVH mutational status and disease course (Hamblin et al., 1999). Patients with a mutated IgVH (M-CLL) often have a good prognosis and may not require treatment, whereas those with unmutated IgVH (UM-CLL) generally have aggressive disease and require earlier intervention. Large scale genomic studies have revealed that only 1% of genes show altered expression between M-CLL and UM-CLL (Rosenwald et al., 2001, Klein et al., 2001), however, proteomic studies identified 8% of proteins to be differentially expressed between the two groups (Alsagaby et al., 2014, Eagle et al., 2015, Barnidge et al., 2005, Glibert et al., 2014). These proteomic studies identified proteins from B-CLL cells isolated from the peripheral blood but the proteome of these cells varies when compared to cells isolated from the proliferative compartments of the bone marrow and lymph nodes (Jaksic et al., 2004, Lampert et al., 1999, Smit et al., 2007).

In this study, we have conducted a global quantitative protein analysis on samples isolated from bone marrow mononuclear cells (BMMNC) with matched samples from peripheral blood mononuclear cells (PBMC) from CLL patients with either UM-IgVH or M-IgVH. The findings of this study may provide further insight into the molecular differences that occur between these two very important prognostic groups.