Problems with interphase fluorescence in situ hybridization in detecting BCR/ABL-positive cells in some patients using a novel technique with extra signals.
Interphase fluorescence in situ hybridization (I-FISH) is frequently used to monitor the response to therapy in various hematological malignancies. We performed a comparison of I-FISH, metaphase FISH (C-FISH), conventional cytogenetics, spectral karyotyping (SKY) and PCR for the detection of the t(9;22) and the BCR/ABL rearrangement in 32 patients with chronic myelogenous leukemia (CML). FISH was done using a novel commercial probe set (VYSIS LSI BCR/ABL ES), which is designed to reduce the rate of false-positive results by marking the argininosuccinate synthetase (ASS) gene and thus providing an extra signal on chromosome 9. Our data indicate, that a substantial number of BCR/ABL-positive patients (n=5 patients, 3 with Ph, 2 with masked Ph) present negative results using this probe set in I-FISH analyses, because they did not fulfill the scoring criteria. In fact, the ASS region, which usually remains on 9q in Ph+ CML, appears to be lost or translocated. Due to these results we recommend that the initial diagnosis as well as the follow-up of patients with Ph+ leukemias should not be based on a single technique but should integrate results of cytogenetics and molecular biology.
Mohr
B
B
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
Bornhäuser
M
M
Platzbecker
U
U
Freiberg-Richter
J
J
Naumann
R
R
Prange-Krex
G
G
Mohm
J
J
Kroschinsky
F
F
Ehninger
G
G
Thiede
C
C
D001853:Bone Marrow / Q000473:pathology; D002871:Chromosome Banding; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007399:Interphase; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008677:Metaphase; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
D016044:Fusion Proteins, bcr-abl