Can Minor bcr/abl Translocation in Acute Leukemia Be Discriminated from Major bcr/abl by Modified FISH Analysis?

Lee, Dong Soon; Cho, Han Ik

Abstract

BACKGROUND: Bcr/abl translocation is a recurring chromosome aberration in acute leukemia (AL). About half of the translocation in AL occur at minor bcr region (m-bcr) and remaining half at major bcr region (M-bcr). PCR method has been the practical tool for this discrimination. Recently, modified probe of FISH (fluorescence in situ hybridization) for bcr/abl was designed. In this study, we investigated whether FISH analysis with this new probe can discriminate between m-bcr and M-bcr.
METHODS
Fourteen cases harboring m-bcr confirmed by qualitative PCR method were enrolled for this study. Except for two cases, all were diagnosed as AL. Cytogenetic results showed Philadelphia chromosome (Ph) in 10 cases all of which the diagnosis was AL. FISH analysis was performed on the archival samples for cytogenetic study in all cases.
RESULTS
Eleven out of 14 cases showed bcr/abl translocation signals by FISH. It was of note that all of these translocation signals were different from those seen in M-bcr with thesame probe. The point of breakage onto the hybridized probe for bcr region made the difference. The resultant number of fusion signal is two in m-BCR and one in M-bcr. All Ph- positive cases showed m-bcr FISH signals. One case of Ph-negative AL in remission was m-bcr-positive by FISH. Remaining three cases of Ph-negative were bcr/abl-negative by FISH.
CONCLUSION
With recently designed bcr/abl FISH probe, m-bcr was clearly discriminated from M-bcr. In addition, one case of AL in morphological and cytogenetic remission and positive for m-bcr by PCR was revealed to have significant amount of residual leukemic cells by FISH. These results demonstrate that FISH can be a powerful tool for the detection and quantitative analysis of m-bcr both at initial diagnosis and follow-up thereafter.