Title |
Development of Real-Time Quantitative Polymerase Chain Reaction Assays to Track Treatment Response in Retinoid Resistant Acute Promyelocytic Leukemia
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Published in |
Frontiers in oncology, January 2011
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DOI | 10.3389/fonc.2011.00035 |
Pubmed ID | |
Authors |
Jelena V. Jovanovic, Kristian Rennie, Dominic Culligan, Andrew Peniket, Anne Lennard, Justin Harrison, Paresh Vyas, David Grimwade |
Abstract |
Molecular detection of minimal residual disease (MRD) has become established to assess remission status and guide therapy in patients with ProMyelocytic Leukemia-RARA+ acute promyelocytic leukemia (APL). However, there are few data on tracking disease response in patients with rarer retinoid resistant subtypes of APL, characterized by PLZF-RARA and STAT5b-RARA. Despite their rarity (<1% of APL) we identified 6 cases (PLZF-RARA, n = 5; STAT5b-RARA, n = 1), established the respective breakpoint junction regions and designed reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) assays to detect leukemic transcripts. The relative level of fusion gene expression in diagnostic samples was comparable to that observed in t(15;17) - associated APL, affording assay sensitivities of ∼1 in 10(4)-10(5). Serial samples were available from two PLZF-RARA APL patients. One showed persistent polymerase chain reaction positivity, predicting subsequent relapse, and remains in CR2, ∼11 years post-autograft. The other, achieved molecular remission (CRm) with combination chemotherapy, remaining in CR1 at 6 years. The STAT5b-RARA patient failed to achieve CRm following frontline combination chemotherapy and ultimately proceeded to allogeneic transplant on the basis of a steadily rising fusion transcript level. These data highlight the potential of RT-qPCR detection of MRD to facilitate development of more individualized approaches to the management of rarer molecularly defined subsets of acute leukemia. |
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Unknown | 10 | 29% |