Acute Promyelocytic Leukemia: Clinical Relevance of Two Major PML-RARα Isoforms and Detection of Minimal Residual Disease by Retrotranscriptase/Polymerase Chain Reaction to Predict Relapse

• Published in: Blood Vol. 82; no. 4; pp. 1264 - 1269
• Main Authors: Huang, Wei, Sun, Guan-Lin, Li, Xiou-Shong, Cao, Qi, Lu, Yan, Jang, Guo-Sheng, Zhang, Fen-Qin, Chai, Jin-Ren, Wang, Zhen-yi, Waxman, Samuel, Chen, Zhu, Chen, Sai-Juan
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.08.1993; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Child; Child, Preschool; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Cloning, Molecular; Female; Hematologic and hematopoietic diseases; Humans; Leukemia, Promyelocytic, Acute - diagnosis; Leukemia, Promyelocytic, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Neoplasm Proteins; Nuclear Proteins; Oncogene Proteins, Fusion - genetics; Polymerase Chain Reaction; Promyelocytic Leukemia Protein; Receptors, Retinoic Acid; Recurrence; Transcription Factors - genetics; Translocation, Genetic; Tumor Suppressor Proteins; Human; Promyelocytic leukemia; Polymerase chain reaction; Residual tumor; Treatment; Acute; Exploration; Remission; Malignant hemopathy; Gene expression
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.4.1264.1264

Recent data have shown that the PML-RARα 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-RARα 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 posi-tivity. These results show that a positive RT/PCR of PML-RARα is a sensitive predictor of relapse in APL.