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Highly Sensitive Fluorescence In Situ Hybridization Method to
Detect Double BCR/ABL Fusion and Monitor Response to Therapy in
Chronic Myeloid Leukemia
Gordon W. Dewald,
William A. Wyatt,
Amy L. Juneau,
Richard O. Carlson,
Alan R. Zinsmeister,
Syed M. Jalal,
Jack L. Spurbeck, and
Richard T. Silver
From the Division of Laboratory Genetics and the Section of
Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, MN; and the
Chronic Myeloid Leukemia National Study Group, Coordinating Center, New
York Hospital-Cornell Medical Center, New York, NY.
We investigated a new method using fluorescence in situ
hybridization and DNA probes that span the common breakpoints of
t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in
bone marrow cells with this translocation, one on the abnormal
chromosome 9 and one on the Philadelphia chromosome (Ph
chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes.
Based on 200 nuclei from each of 30 normal specimens, the mean
percentage of false-positive cells was 0.25 ± 0.39. Thirty-seven
specimens from 10 patients were studied before treatment and two or
more times at 4-month intervals after treatment with
interferon- 2b (IFN-2b) with or without
ara-C. Based on 200 nuclei, the results of D-FISH in these specimens
correlated closely with quantitative cytogenetics and accurately
quantified disease within a few percent. We studied 6,000 nuclei for
each of six specimens, three normal and three from patients with
chronic myeloid leukemia (CML) in cytogenetic remission. The normal
cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic
remission had residual disease ranging from 7 (0.117%) to 53 (0.883%)
Ph-positive nuclei. We conclude that D-FISH can detect the Ph
chromosome and its variant translocations and accurately quantify
disease in CML at diagnosis and at all times after treatment, including
cytogenetic remission.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3357-3365
© 1998 by The American Society of Hematology.
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