Feasibility and clinical significance of real-time quantitative RT-PCR assay of PML-RARalpha fusion transcript in patients with acute promyelocytic leukemia.

Abstract

INTRODUCTION:

To study the relationship between the expression level of the PML-RARalpha fusion transcripts and the clinical status and efficiency of the therapy in acute promyelocytic leukemia (APL) patients, we applied a very sensitive and specific real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) system to quantify the dose of PML-RARalpha fusion transcripts in a series of APL patients at distinct disease stages.

MATERIALS AND METHODS:

A total of 31 APL patients (19 males and 12 females; aged from 8 to 74 years) from eight hospitals in Shanghai were analysed. Real-time Quantitative RT-PCR was used to measure the normalized dose (DoseN) of PML-RARalpha fusion transcripts.

RESULTS:

A wide range of PML-RARalpha DoseN above 1 x 10(3) was noted in 25 newly diagnosed patients. PML-RARalpha DoseN was significantly decreased after remission induction with ATRA, ATRA/chemotherapy or As2O3 and further reduced after consolidation. The fact that all patients with long disease free survival had a constantly low PML-RARalpha DoseN below 2 x 10(2) and a higher level predicted impending relapse suggests that this value could serve as a 'threshold' for molecular remission. PML-RARalpha DoseN was also of prognostic value in a group of relapsed patients, since good response to As2O3 reinduction was accompanied by a remarkable reduction of fusion transcript level, whereas patients with high PML-RARalpha Dose(N) after the second CR tended to relapse again rapidly.

CONCLUSION:

These results confirm that real-time RT-PCR assay for PML-RARalpha transcripts in APL patients is useful in reflecting leukemic burden, assessing response to treatment and indicating the ultimate clinical outcome or curability of disease.

• Authors: B W Gu, J Hu, L Xu, H Yan, W R Jin, Y M Zhu, W L Zhao, C Niu, Q Cao, X Y Su, J Gu, H Y Ying, Y Chen, S M Xiong, Z X Shen, Z Chen, S J Chen
• Journal: The hematology journal : the official journal of the European Haematology Association (Hematol J) Vol. 2 Issue 5 Pg. 330-40 ( 2001) ISSN: 1466-4860 [Print] England
• PMID: 11920269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Neoplasm Proteins
• Oncogene Proteins, Fusion
• RNA, Messenger
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (administration & dosage)
• Bone Marrow (pathology)
• Child
• Disease Progression
• Disease-Free Survival
• Feasibility Studies
• Female
• Humans
• Leukemia, Promyelocytic, Acute (diagnosis, drug therapy, genetics)
• Male
• Middle Aged
• Neoplasm Proteins (analysis, genetics)
• Neoplasm, Residual (diagnosis, genetics)
• Oncogene Proteins, Fusion (analysis, genetics)
• Prognosis
• RNA, Messenger (analysis)
• Reproducibility of Results
• Reverse Transcriptase Polymerase Chain Reaction (standards)
• Sensitivity and Specificity