PMID- 9739013 OWN - NLM STAT- MEDLINE DCOM- 19990413 LR - 20131121 IS - 1045-2257 (Print) IS - 1045-2257 (Linking) VI - 23 IP - 2 DP - 1998 Oct TI - A two-color BCR-ABL probe that greatly reduces the false positive and false negative rates for fluorescence in situ hybridization in chronic myeloid leukemia. PG - 109-15 AB - The t(9;22) translocation resulting in the fusion of BCR and ABL genes is pathognomonic in chronic myeloid leukemia (CML) and may be investigated at the molecular level using fluorescence in situ hybridization (FISH). Two-color BCR-ABL probes visualizing one fusion signal (1F FISH) have high false positive rates (FPR) and false negative rates (FNR). The FPR is a result of the random spatial association of probe signals within normal interphase cells so that some cells appear to contain the BCR-ABL fusion gene. The FNR of 1F FISH probes depends on the distance between the BCR and ABL probes hybridized to the BCR-ABL fusion gene (< or =368 kb); the "gap" between the signals causing the cell to be interpreted as normal. To overcome these difficulties, a two-color probe was used, employing four yeast artificial chromosome (YAC) sequences that span the breakpoint regions of the BCR and ABL genes and that visualize the two fusion signals BCR-ABL and ABL-BCR in CML cells (2F FISH). The FNR for the 2F FISH probes was assessed on clonal Ph+ granulocyte-macrophage-colony-forming cell (CFU-GM) derived colonies and was reduced to 0.4% (2/450), compared with an FNR of 13.5% (111/823) with 1F FISH. The FPR in normal mononuclear cells for the 2F FISH was 0. 19 +/- 0.12% (3/1,700), whereas the FPR using 1F FISH was 4.5 +/- 2.3% (63/1,294). The 2F FISH can thus be used to evaluate very small frequencies of BCR-ABL-positive and -negative interphase cells and may be of use in the clinical monitoring of CML. FAU - Grand, F H AU - Grand FH AD - Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom. FAU - Chase, A AU - Chase A FAU - Iqbal, S AU - Iqbal S FAU - Nguyen, D X AU - Nguyen DX FAU - Lewis, J L AU - Lewis JL FAU - Marley, S B AU - Marley SB FAU - Davidson, R J AU - Davidson RJ FAU - Goldman, J M AU - Goldman JM FAU - Gordon, M Y AU - Gordon MY LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (DNA Probes) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) SB - IM MH - Adult MH - Aged MH - Chromosomes, Artificial, Yeast/genetics MH - DNA Probes/*genetics MH - False Negative Reactions MH - False Positive Reactions MH - Female MH - Fusion Proteins, bcr-abl/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics MH - Leukocyte Count MH - Leukocytes, Mononuclear/chemistry MH - Male MH - Middle Aged MH - Sensitivity and Specificity EDAT- 1998/09/17 02:03 MHDA- 2000/06/20 09:00 CRDT- 1998/09/17 02:03 PHST- 1998/09/17 02:03 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1998/09/17 02:03 [entrez] AID - 10.1002/(SICI)1098-2264(199810)23:2<109::AID-GCC3>3.0.CO;2-6 [pii] PST - ppublish SO - Genes Chromosomes Cancer. 1998 Oct;23(2):109-15.