Introduction

Leukaemic transformation results from genetic alterations giving rise to CLL cells that show resistance to apoptosis and therefore accumulate (Hallek, 2017). Tumour burden is also exacerbated by the increased rate of proliferation of CLL cells which occurs in distinct tissue areas at a clonal birth rate of 1–2% per day (Efremov & Laurenti, 2014; Ten Hacken & Burger, 2014).

CLL is highly heterogeneous in terms of both pathobiology and clinical course, with some patients having progressive disease requiring therapy soon after diagnosis whilst others have indolent disease in which treatment can be delayed for many years (Zhang & Kipps, 2014). In approximately 50% of cases, associated with more aggressive disease, immunoglobulin (Ig) expressed in leukaemic cells is encoded by unmutated immunoglobulin heavy-chain variable-region (IGHV) genes whereas indolent CLL tends to be associated with cells expressing immunoglobulin encoded by mutated IGHV genes (Zhang & Kipps, 2014).

A complex interplay of specific genetic aberrations and microenvironmental signals, especially involving bone marrow stromal cells, nurse-like cells and T cells, drive the proliferation and survival of CLL cells (Efremov & Laurenti, 2014; Ten Hacken & Burger, 2014). Expansion and survival of the CLL clone, as well as drug resistance, is facilitated by interactions between CLL surface molecules (e.g. the B cell receptor [BCR], chemokine receptors, adhesion molecules, tumour necrosis factor [TNF] receptor family molecules) and their respective tissue ligands (Ten Hacken & Burger, 2014).