Atypical BCR and ABL D-FISH patterns in chronic myeloid leukemia and theirpossible role in therapy

D-FISH uses DNA probes with fluorescence in situ hybridization to detect tw o fusion signals in cells with a t(9;22)(q34;q11.2) from patients with chro nic myeloid leukemia (CML). Using D-FISH, 147 patients with CML were studie d and considerable macro genetic Variation was observed among their Ph-chro mosomes. Typical D-FISH signal patterns were observed for 81% of patients, but three different atypical patterns were seen in 19% of patients. Atypica l patterns among Ph-chromosomes were consistent with loss of the 3' portion of BCR that is usually translocated to chromosome 9, or loss of the 5' seg ment of ABL that usually remains on chromosome 9, or loss of both the 3' tr anslocated BCR and 5' residual ABL hybridization sites. Atypical patterns w ere associated with all forms of Ph-chromosomes including t(9;22)(q34;q1,2) , complex translocations and masked. The normal range for 500 interphase nu clei for patients with typical patterns is <1%. By comparison, the normal r ange for patients with either of two atypical patterns was less than or equ al to 1.8% and for patients with the other atypical pattern was less than o r equal to 23%. Thus, special scoring criteria are needed to detect and qua ntify nuclei with atypical patterns using D-FISH. The proportion of patient s that responded to therapy with interferon alpha-2b or interferon alpha-2b and ara-C for 36 patients with typical patterns was similar to 7 patients with atypical patterns.