Molecular diagnosis and monitoring of acute promyelocytic leukemia treated with retinoic acid.
The characteristic balanced 15;17 translocation, t(15;17), of acute promyelocytic leukemia (APL) fuses the retinoic acid receptor alpha (RAR alpha) gene on chromosome 17 to PML, a recently described gene of unknown function, on chromosome 15. It is this fusion gene and consequent fusion protein that is thought to be responsible for both the block in normal myelocyte differentiation as well as the dramatic in vitro and in vivo response to the differentiating effects of all-trans retinoic acid (RA). The t(15;17) also provides a genetic marker for the presence of leukemic cells. PML/RAR alpha fusion mRNA's can be detected by a reverse transcription polymerase chain reaction (RT-PCR) assay. Using this assay, at least three distinct patterns, differing in the 3' region of the PML breakpoint, can be identified. The detection of abnormal mRNA's by the RT-PCR assay has proven to be an important aid in the diagnosis of APL as well as the best predictor of an initial clinical response to RA. The results of an ongoing, longitudinal evaluation of patients with APL show that the RT-PCR assay may also be a useful indicator of minimal residual disease (MRD). Negative RT-PCR assays following completion of all therapy are associated with prolonged disease free survival, whereas persistence or return of a positive test is highly correlated with subsequent relapse. Further studies will determine whether patients who test positive may benefit from the introduction of additional antileukemic therapy.
Levine
K
K
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
DeBlasio
A
A
Miller
W H
WH
D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D014212:Tretinoin