Immunoglobulin heavy chain gene fingerprinting reveals widespread oligoclonality in B-lineage acute lymphoblastic leukaemia.

Abstract

Acute lymphoblastic leukaemia (ALL) of B-cell lineage typically arises as a monoclonal expansion of committed B-lymphocyte precursors that are arrested at an immature stage of differentiation. From Southern hybridization analysis of immunoglobulin heavy chain (IgH) genes in leukaemic blasts, the occurrence of a sizeable minority of patients displaying multiple (greater than two) rearranged heavy chain alleles has been widely reported. In at least some patients these data are consistent with the presence of oligoclonal populations of precursor B-cells. We have used a more sensitive, polymerase chain reaction based immunoglobulin gene 'fingerprinting' approach in the analysis of B-cell clonality in eight patients with common ALL which were apparently monoclonal on the basis of Southern blot analysis of their IgH genes. The results revealed an oligoclonal pattern of IgH gene rearrangement in half of the patients analysed, implying that oligoclonality at the level of B-cell commitment, as defined by IgH gene rearrangement, is much more widespread in this disease than has previously been recognized.