Abstract
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. × 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 104 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.
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Kasprzyk, A., Secker-Walker, L. Increased sensitivity of minimal residual disease detection by interphase FISH in acute lymphoblastic leukemia with hyperdiploidy. Leukemia 11, 429–435 (1997). https://doi.org/10.1038/sj.leu.2400589
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DOI: https://doi.org/10.1038/sj.leu.2400589