title: Increased sensitivity of minimal residual disease detection by interphase FISH in acute lymphoblastic leukemia with hyperdiploidy.
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. 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.
authors.affiliation: Department of Haematology, The Royal Free Hospital School of Medicine, Hampstead, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kasprzyk
authors.forename: L M
authors.initials: LM
authors.lastname: Secker-Walker
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D004171:Diploidy; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007399:Interphase; D007621:Karyotyping; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D012680:Sensitivity and Specificity