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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-05-1357. This Article Full Text (PDF) All Versions of this Article: 2002-05-1357v1 101/7/2521    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gallagher, R. E Articles by Willman, C. L Search for Related Content PubMed PubMed Citation Articles by Gallagher, R. E Articles by Willman, C. L Social Bookmarking                   What's this? Submitted May 9, 2002 Accepted November 15, 2002 Quantitative real-time RT-PCR analysis of PML-RAR mRNA in acute promyelocytic leukemia: Assessment of prognostic significance in adult patients from intergroup protocol 0129 Robert E Gallagher*, Beow Y Yeap, Wanli Bi, Kenneth J Livak, Nike Beaubier, Sreenivas Rao, Clara D Bloomfield, Frederick R Appelbaum, Martin S Tallman, James L Slack, and Cheryl L Willman Department of Oncology, Montefiore Medical Center and Albert Einstein Cancer Center, Bronx, NY, USA Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Applied Biosystems, Inc., Foster City, CA, USA Departments of Pathology and Cell Biology, University of New Mexico, Albuquerque, NM, USA The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Chicago, IL, USA Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA * Corresponding author; email: rgallagh{at}aecom.yu.edu. The potential prognostic value of quantitative real-time RT-PCR (qrtPCR) measurements of PML-RAR mRNA in acute promyelocytic leukemia was retrospectively assessed before treatment and at 3 post-treatment intervals in 123 patients treated on intergroup protocol 0129. The primary measure was the PML-RARGAPDH normalized quotient (NQ), i.e., PML-RAR mRNA copies/GAPDH mRNA copies. Only samples with >2.5x105 copies of the housekeeping gene glyceraldehyde-3'-phosphate dehydrogenase (GAPDH) (detection sensitivity >104) were considered NQ evaluable. Using RNA from low-density selected cells, paired peripheral blood (PB) and bone marrow (BM) samples (N=140) had comparable NQ values (p<.001). Pretreatment, high NQ was associated with short(S)-form PML-RAR (p<.001) but not with white blood cell count or clinical outcome. Following treatment, NQ was lower in all-trans retinoic acid-induced than chemotherapy-induced patients both at complete remission (CR; p=.018) and at first test post-consolidation chemotherapy (PCC; p=.037). At PCC, patients with NQ >10-5 had 4.1-fold increased relapse risk (p=.008); however, 73% of patients who relapsed had NQ <10-5. In the follow-up period (FUP), any NQ value >10-5 had 17.5-fold and >10-6 had 7.6-fold increased relapse risk (p<.001), while no gradation of relapse-risk (~18%) could be identified at NQ <10-6, including NQ-negative. These results indicate that qrtPCR monitoring of PML-RAR NQ can identify patients at high risk of relapse and suggest that clinically-practical PB NQ monitoring at more frequent FUP intervals may improve predictive accuracy for relapse or continuing CR in many patients with persistent, fluctuating minimal residual disease levels. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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