Detection of Long and Short isoforms of PML-RARA mRNA by RT-PCR in Acute Promyelocytic Leukemia / 대한혈액학회지

ABSTRACT

BACKGROUND: Chromosomal translocation t (15 ; 17), the breakpoints of which are in the PML gene on chromosome 15 and RARA gene on chromosome 17, is specifically found in acute promyelocytic leukemia (APL). According to the site of breakpoint on PML gene, two major isoforms (Long or Short) of PML-RARA mRNA are produced. METHODS: To detect long (L) and short (S) isoforms, we extracted RNA and amplified PML-RARA mRNA by RT-PCR from leukemic cells of 20 cases of APL. We compared the result of cytogenetic study and the clinical response after chemotherapy or ATRA therapy for remission induction with the isoforms of PML-RARA mRNA. RESULTS: In 19 cases (94%) among 20 cases with APL, PML-RARA mRNA was positive, and negative in a case who showed only i (17q) without t (15;17). In 12 cases (63.2%), L isoform of PML-RARA mRNA was detected, and S isoform (36.8%) in 7 cases of APL. All the cases with t (15;17) were positive for PML-RARA mRNA. In a case of trisomy 8 without t (15;17), PML-RARA mRNA of L isoform was detected. There was no significant difference between L and S isoform in laboratory findings and clinical response after chemotherapy or ATRA treatment. Excluding 6 cases with death before or within 10 days of ATRA treatment or chemotherapy, among 13 patients of positive PML-RARA mRNA, 11 cases (84.6%) reached to complete remission, but a case of negative PML-RARA mRNAwas resistent to ATRA treatment. CONCLUSION: This study suggests that detection of PML-RARA mRNA with two major isofroms using RT-PCR is more sensitive to diagnose APL and to detect minimal residual disease than cytogenetic study and that further study with more cases may be substantiated the types of PML-RARA mRNA isoform as a prognostic marker.