Leukaemia presenting as marrow hypoplasia: molecular detection of the leukaemic clone at the time of initial presentation.

Occasional cases of transient marrow hypoplasia in childhood evolve into acute leukaemia. We studied two children who presented with marrow hypoplasia following infection and who developed acute lymphoblastic leukaemia 2-3 months later. A simple polymerase-chain-reaction (PCR) test for monoclonality showed that immunoglobulin heavy-chain gene rearrangements of the same size were present at the times of both hypoplasia and leukaemia, and DNA sequencing confirmed identity of these rearrangements. PCR-based quantification, using patient-specific primers, showed in both patients that the leukaemic clone made up 20-25% of the marrow cells during hypoplasia. In contrast, four patients with typical aplastic anaemia showed only polyclonal B-cell populations in the marrow. We conclude that the leukaemic clone was already present at the time of hypoplasia in the two index patients and that in future a simple PCR test for monoclonality could be used to screen patients with marrow aplasia or hypoplasia for the presence of a monoclonal B-cell population. Patients with monoclonal populations could then be monitored carefully for subsequent development of leukaemia.