Interpretation

The assay incorporates 2 parts: a qualitative screen for exon 12 NPM1 alterations and a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay to determine the copy number of NPM1 transcripts (relative to ABL1 reference messenger RNA [mRNA]). This strategy will allow for identification of the NPM1 alteration at diagnosis, as well as a high sensitivity method to monitor patients who are post-therapy for minimal residual disease. Results will therefore be interpreted with integration of the quantitative and qualitative test results in the context of NPM1 alteration type identified at the time of AML diagnosis if available. Because the quantitative RT-PCR component only reliably detects and quantifies the 3 most common variant types (A, B, D), there is a very small possibility that the qualitative assay may indicate the presence of an NPM1 alteration, but the quantitative assay will be (falsely) negative. In patients with newly diagnosed acute myeloid leukemia, a normal karyotype, and no FLT3 variant, the presence of an NPM1 alteration is an indicator of a more favorable prognosis. Similarly, following chemotherapy, the presence, relative quantity, and trend of change of NPM1 mRNA transcript is associated with risk of disease relapse.