title: Leukaemia presenting as marrow hypoplasia: molecular detection of the leukaemic clone at the time of initial presentation.
abstract: 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.
authors.affiliation: Department of Haematology, Flinders University and Medical Centre, Bedford Park, South Australia.
authors.forename: A A
authors.initials: AA
authors.lastname: Morley
authors.forename: M J
authors.initials: MJ
authors.lastname: Brisco
authors.forename: M
authors.initials: M
authors.lastname: Rice
authors.forename: L
authors.initials: L
authors.lastname: Snell
authors.forename: L M
authors.initials: LM
authors.lastname: Peng
authors.forename: E
authors.initials: E
authors.lastname: Hughes
authors.forename: S H
authors.initials: SH
authors.lastname: Neoh
authors.forename: P J
authors.initials: PJ
authors.lastname: Sykes
mesh_terms: D000741:Anemia, Aplastic / Q000209:etiology / Q000235:genetics; D001855:Bone Marrow Diseases / Q000209:etiology* / Q000235:genetics; D002675:Child, Preschool; D002999:Clone Cells; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000235:genetics; D012141:Respiratory Tract Infections / Q000150:complications*