Lo-Coco Figure 2.
Lo-Coco Figure 2. Serial MRD monitoring for the PML-RARα fusion by real-time quantitative RT-PCR (RQ-PCR). / This figure demonstrates fluctuation in PML-RARα transcript copy numbers normalized to ABL (bold blue line) in serial marrow samples taken over the treatment course of this patient, initially treated in the UK MRC AML12 trial. The sensitivity for each assay is calculated on the basis of ABL expression in the given sample and the difference in Cycle threshold value (ΔCt) between PML-RARα and ABL at diagnosis and is denoted by the dotted line. Samples testing PCR positive are indicated by filled blue circles and PCR negative by white circles (for samples testing PCR negative, the sensitivity and normalized fusion gene copy number data points are superimposed). This analysis demonstrates the advantages of RQ-PCR to investigate kinetics of molecular response and relapse, as well as identifying poor quality samples likely to give “false negative” results. A 3-log reduction in PML-RARα transcript level was observed following induction; the post-course 2 sample afforded a sensitivity of <1 in 500 and hence yielded a “false-negative” PCR result. The patient was retreated at the point of molecular relapse with arsenic trioxide (ATO), which led to a net reduction in PML-RARα fusion transcript levels. The patient was considered unfit for further intensive therapy at that stage; subsequent sequential monitoring revealed a steady rise in PML-RARα transcript levels, successfully predicting a frank hematological relapse within 5 months. The patient received re-induction therapy, achieving PCR negativity at a sensitivity of 1 in 1000. Further recurrence of PCR positivity predicted a subsequent relapse. / (Figure courtesy of D.Grimwade, Y. Hasan and E. Nugent).

Serial MRD monitoring for thePML-RARα fusion by real-time quantitative RT-PCR (RQ-PCR).

This figure demonstrates fluctuation in PML-RARα transcript copy numbers normalized to ABL (bold blue line) in serial marrow samples taken over the treatment course of this patient, initially treated in the UK MRC AML12 trial. The sensitivity for each assay is calculated on the basis of ABL expression in the given sample and the difference in Cycle threshold value (ΔCt) between PML-RARα and ABL at diagnosis and is denoted by the dotted line. Samples testing PCR positive are indicated by filled blue circles and PCR negative by white circles (for samples testing PCR negative, the sensitivity and normalized fusion gene copy number data points are superimposed). This analysis demonstrates the advantages of RQ-PCR to investigate kinetics of molecular response and relapse, as well as identifying poor quality samples likely to give “false negative” results. A 3-log reduction in PML-RARα transcript level was observed following induction; the post-course 2 sample afforded a sensitivity of <1 in 500 and hence yielded a “false-negative” PCR result. The patient was retreated at the point of molecular relapse with arsenic trioxide (ATO), which led to a net reduction in PML-RARα fusion transcript levels. The patient was considered unfit for further intensive therapy at that stage; subsequent sequential monitoring revealed a steady rise in PML-RARα transcript levels, successfully predicting a frank hematological relapse within 5 months. The patient received re-induction therapy, achieving PCR negativity at a sensitivity of 1 in 1000. Further recurrence of PCR positivity predicted a subsequent relapse.

(Figure courtesy of D.Grimwade, Y. Hasan and E. Nugent).

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