title: RARA fluorescence in situ hybridization overcomes the drawback of PML/RARA fluorescence in situ hybridization in follow-up of acute promyelocytic leukemia.
abstract: Determination of the remission of acute promyelocytic leukemia (APL) after chemotherapy can be difficult because many cases of APL show reverse transcription polymerase chain reaction positivity after consolidation treatment. Moreover, the discrimination of leukemic promyelocytes and regenerating promyelocytes by morphology is sometimes difficult. Although PML/RARA fluorescence in situ hybridization (FISH) can help, the major drawback of FISH is its high false positive rate, which reaches up to 5-10%. We used RARA FISH at the initial diagnosis (16 cases) and follow-up of APL patients (21 cases) with t(15;17), though RARA FISH was originally designed to detect translocations involving the RARA gene rather than t(15;17), and compared the results with those of PML/RARA FISH. A reference range for PML/RARA and RARA FISH was set using 50 normal control specimens. Using a RARA split probe, we were able to lower the reference range for RARA rearrangement down to 1.5%, which is significantly lower than that of PML/RARA (8%). Actually 74.2% (46/62 cases) of cases with positive signals of the PML/RARA rearrangement by the PML/RARA probe, showed absolutely negative results with the RARA split probe. By conducting RARA FISH, we were able to significantly resolve the difficulty in interpreting results around cut-off value in PML/RARA FISH. In conclusion, we believe that once the PML/RARA rearrangement is confirmed either by G-banding or FISH, RARA FISH is more effective than PML/RARA during the follow-up of APL after treatment.
authors.affiliation: Department of Clinical Pathology, Seoul National University College of Medicine, Seoul, South Korea. soonlee@plaza.snu.ac.kr
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
authors.forename: Yun Song
authors.initials: YS
authors.lastname: Lee
authors.forename: Young Ree
authors.initials: YR
authors.lastname: Kim
authors.forename: Kyu Sup
authors.initials: KS
authors.lastname: Han
authors.forename: Kyoung Un
authors.initials: KU
authors.lastname: Park
authors.forename: Cha Ja
authors.initials: CJ
authors.lastname: She
authors.forename: Eu Chong
authors.initials: EC
authors.lastname: Kim
authors.forename: Sun Yang
authors.initials: SY
authors.lastname: Park
authors.forename: Han Ik
authors.initials: HI
authors.lastname: Cho
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001773:Blood Cells / Q000648:ultrastructure; D001854:Bone Marrow Cells / Q000648:ultrastructure; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics / Q000648:ultrastructure*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000648:ultrastructure*; D018450:Disease Progression; D005189:False Positive Reactions; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein