BACKGROUND: The most noted rearrangement identified in acute promyelocytic leukemia (APL) involves the PML and RARa genes, which results in the formation of the PML/RARa gene fusion. In the fluorescence in situ hybridization (FISH) for PML/RARa, the two signals may coincidentally overlap in normal nuclei. We investigated whether a new RARa rearrangement probe could discriminate the false-positive fusion signal of the PML/RARa translocation probe. METHODS: A total of 51 cases, which showed the results from 1% to the borderline level by PML/ RARa FISH, were re-tested with the RARa rearrangement probe. Also, we compared the RARa FISH with the PML/RARa FISH on 16 patients with newly diagnosed APL and performed the RARa FISH on 20 bone marrow specimens without hematologic malignancies in order to set up the cut-off value. RESULTS: The cut-off for the RARa FISH was determined as 1.02%. For patients with newly diagnosed APL, the PML/RARa FISH showed positive signals in 95.3+/-6.5% of the cells and RARa FISH showed positive signals in 97.0+/-7.0% (r=0.83). Of a total of 41 cases consisting of hematological disorders other than APL, five cases showed results equal to or greater than 5% with PML/RARa FISH and one case showed a positive result with RARa FISH. Of 10 follow-up APL cases, seven cases showed results equal to or greater than 5% with the PML/RARa FISH and four cases showed positive results with the RARa FISH. CONCLUSIONS: The cut-off value for the RARa FISH is 1.02% and we consider RARa FISH as the proper method for follow-up of APL.
Bone Marrow ; Fluorescence* ; Follow-Up Studies* ; Gene Fusion ; Hematologic Neoplasms ; Humans ; In Situ Hybridization* ; Leukemia, Promyelocytic, Acute*

BACKGROUND: The complementary ABL-BCR gene rearrangement is formed at chromosome 9 parallel to the Ph chromosome at der(22)t(9;22), which has been found deleted in a minority of chronic myelogenous leukemia (CML) patients. This study was designed to analyze the deletion status of ABL and/or BCR on derivative chromosome 9 and to evaluate the prognostic significance of the deletion of these genes in CML. METHODS: We studied 79 patients who were diagnosed as CML at Seoul National University Hospital between January 1997 and February 2002. The deletion status of ABL and BCR on derivative chromosome 9 was investigated by interphase fluorescent in situ hybridization (FISH) method. RESULTS: ABL deletion was detected in 14 (17.7%) patients and BCR deletion was observed in 8 patients (10.1%). Event-free survival time of the patients with ABL and/or BCR deletion (19.0%) was shorter than that of the patients without any deletion of these two genes (median, 40.0 months vs. 92.0 months)(P=0.027). Twenty seven patients progressed to blast crisis in this period. The period to blast crisis was also shorter in 8 patients with ABL and/or BCR deletion than in 19 patients without any gene deletion (P=0.044). The b2a2 mRNA type was more frequent in the patients with ABL deletion only than in the patients without any gene deletion (P=0.034). CONCLUSIONS: Event-free survival time and the period to blast crisis were significantly shorter in patients with deletion of ABL and/or BCR on derivative chromosome 9. ABL and/or BCR deletion can be a significant prognostic marker that indicates rapid disease progression.
Blast Crisis ; Chromosomes, Human, Pair 9* ; Disease Progression ; Disease-Free Survival ; Gene Deletion ; Gene Rearrangement ; Humans ; Hydrogen-Ion Concentration ; In Situ Hybridization, Fluorescence ; Interphase ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Philadelphia Chromosome ; RNA, Messenger ; Seoul