Acute promyelocytic leukemia: clinical relevance of two major PML-RAR alpha isoforms and detection of minimal residual disease by retrotranscriptase/polymerase chain reaction to predict relapse.
Recent data have shown that the PML-RAR alpha fusion gene resulting from translocation t(15;17) is a highly reliable molecular marker of acute promyelocytic leukemia (APL). In this study performed on 97 Chinese patients with APL, the retrotranscriptase/polymerase chain reaction (RT/PCR) was used to evaluate the clinical relevance of the long (L) or short (S) PML-RAR alpha fusion mRNA isoforms and to study minimal residual disease during clinical remission (CR). There were more early deaths during the all-trans retinoic acid (ATRA) induction treatment and more relapses within 2 years of CR in the S-type (6 of 19 cases) than in the L-type group (2 of 33 cases) (P < .025). Among 12 cases analyzed before and after the ATRA-induced CR, 9 cases (75%) showed positive RT/PCR, whereas only 3 cases showed a negative result, justifying the need for chemotherapy after ATRA-induced CR. Eleven of 62 APL patients in CR, after ATRA-induced CR and chemotherapy consolidation (follow-up, from 3 to 72 months), showed positive RT/PCR. Five of them relapsed within 1 to 6 months after the positive test; one converted to negative after further chemotherapy; and 5 remained in CR status without further PCR data. However, the latter 5 cases all received further intensive consolidation therapy after the PCR positivity. These results show that a positive RT/PCR of PML-RAR alpha is a sensitive predictor of relapse in APL.
Laboratory of Molecular Biology, Shanghai Institute of Hematology, China.
W
W
Huang
G L
GL
Sun
X S
XS
Li
Q
Q
Cao
Y
Y
Lu
G S
GS
Jiang
G S
GS
Jang
F Q
FQ
Zhang
J R
JR
Chai
Z Y
ZY
Wang
S
S
Waxman
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid; D012008:Recurrence; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human