Department of Haematology, The Royal Free Hospital School of Medicine, Hampstead, London, UK.
Interphase fluorescent in situ hybridization (FISH) for the detection of minimal residual disease detection (MRD) in patients with acute lymphoblastic leukemia (ALL) and a high hyperdiploid clone (>50 chromosomes) at diagnosis is presented. By simultaneous targetting of three chromosomes gained, a sensitivity of 10(4) was achieved. Control values (mean + s.d. x 2 of false positive cells in normal peripheral blood) using probes singly, in pairs or as a triplet were 1.4-2.0%, 0.01-0.02% and zero (in 10(4) cells), respectively. A serial dilution experiment mixing control blood lymphocytes with bone marrow from a patient with a >85% cells with >50 chromosomes and probing it with single, dual or triple probes, revealed the clone down to dilutions of 10(-1), 10(-3) and 10(-4), respectively. FISH confirmed chromosomal gains at diagnosis (13 cases) and in relapse (three cases). Positive remission samples (0.01 to 0.06% cells with chromosome gains) were more frequent during the first 7 months (7/12) from diagnosis than later (3/11). Serial studies showed a decline in clone size with time. Conversion from a negative to a positive sample heralded relapse in one case. FISH confirmed an isolated central nervous system relapse and detected a hyperdiploid clone in a chromosomally normal relapse. This technique could be applied whenever three cytogenetic/genetic changes are found.
PMID: 9067585, UI: 97220210