Atypical BCR and ABL D-FISH patterns in chronic myeloid leukemia and their possible role in therapy.
D-FISH uses DNA probes with fluorescence in situ hybridization to detect two fusion signals in cells with a t(9;22)(q34;q11.2) from patients with chronic myeloid leukemia (CML). Using D-FISH, 147 patients with CML were studied and considerable macro genetic variation was observed among their Ph-chromosomes. Typical D-FISH signal patterns were observed for 81% of patients, but three different atypical patterns were seen in 19% of patients. Atypical 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' segment of ABL that usually remains on chromosome 9, or loss of both the 3' translocated BCR and 5' residual ABL hybridization sites. Atypical patterns were associated with all forms of Ph-chromosomes including t(9;22)(q34;q1.2), complex translocations and masked. The normal range for 500 interphase nuclei for patients with typical patterns is < 1%. By comparison, the normal range for patients with either of two atypical patterns was < or = 1.8% and for patients with the other atypical pattern was < or = 23%. Thus, special scoring criteria are needed to detect and quantify nuclei with atypical patterns using D-FISH. The proportion of patients 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.
Dewald
G W
GW
Division of Laboratory Genetics Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
Wyatt
W A
WA
Silver
R T
RT
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003561:Cytarabine / Q000627:therapeutic use; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015513:Oncogene Proteins / Q000235:genetics*; D010677:Philadelphia Chromosome; D011237:Predictive Value of Tests; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D003561:Cytarabine; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr