Interstitial insertion of RARα gene into PML gene in a patient with acute promyelocytic leukemia (APL) lacking the classic t(15;17).
The diagnosis of APL is based on clinical and morphological tests though the final diagnosis is at the molecular level. An accurate diagnosis is important as it mandates targeted therapy to improve survival. We report a case of APL without t(15;17) in conventional cytogenetic study and with initially negative fluorescence in situ hybridization (FISH) study on cells in interphase. Reverse transcription polymerase chain reaction (RT-PCR) for the promyelocytic/retinoic acid receptor alpha gene (PML/RARα) fusion oncogene proved the clinical diagnosis as well as FISH study on cells in metaphase. The cause was a cryptic translocation of the RARα gene into PML. We reviewed 36 additional cases of APL diagnosed in our hospital since 1992. This was the only case that failed to show t(15;17) in cytogenetics. However, three cases with t(15;17) in cytogenetics had negative RT-PCR for PML/RARα. Our case emphasizes that cytogenetics, FISH and RT-PCR studies are complementary studies for the molecular diagnosis of APL.
Goldschmidt
Neta
N
Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. neta@hadassah.org.il
Yehuda-Gafni
Orly
O
Abeliovich
Deborah
D
Slyusarevsky
Elena
E
Rund
Deborah
D
D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C070576:PML protein, human