RARA fluorescence in situ hybridization overcomes the drawback of PML/RARA fluorescence in situ hybridization in follow-up of acute promyelocytic leukemia.
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.
Lee
Dong Soon
DS
Department of Clinical Pathology, Seoul National University College of Medicine, Seoul, South Korea. soonlee@plaza.snu.ac.kr
Lee
Yun Song
YS
Kim
Young Ree
YR
Han
Kyu Sup
KS
Park
Kyoung Un
KU
She
Cha Ja
CJ
Kim
Eu Chong
EC
Park
Sun Yang
SY
Cho
Han Ik
HI
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
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