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Recurrent mutations in JAK2 and MPL genes are genetic hallmarks of BCR-ABL1–negative myeloproliferative neoplasms. Detection of JAK2 and MPL mutations has been incorporated into routine diagnostic algorithms for these diseases. This Special Article summarizes results from a nationwide laboratory survey of JAK2 and MPL mutation analysis. Based on the current practice pattern and the literature, this Special Article provides recommendations and guidelines for laboratory practice for detection of mutations in the JAK2 and MPL genes, including clinical manifestations for prompting the mutation analysis, current and recommended methodologies for testing the mutations, and standardization for reporting the test results. This Special Article also points to future directions for genomic testing in BCR-ABL1–negative myeloproliferative neoplasms.

The BCR-ABL1 translocation is a hallmark of chronic myeloid leukemia. Because patients treated with imatinib and other tyrosine kinase inhibitors achieve lower levels of detectable disease, quantitation of BCR-ABL1 transcripts with quantitative RT-PCR has become an essential tool in chronic myeloid leukemia monitoring. The prognostic significance of molecular responses was recently established by large-scale clinical trials. Achieving defined levels of BCR-ABL1 on the International Scale within specific time frames is an important measure for assessing patient response and probability for relapse and progression. However, extensive variation in quantitative RT-PCR procedures and reporting makes it difficult to interpret these results. More important, lack of standardization, particularly in the United States, prevents the comparison of individual patient results to the data from the clinical trials, which thereby prohibits the meaningful use of such results in the direction of patient care. In this article, we will present an overview of the clinical trial discoveries that drive the need for standardization, review the most updated monitoring guidelines by the National Comprehensive Cancer Network, and highlight recommendations for laboratory practice regarding internal controls and reference materials. Finally, we will provide an update on the recent efforts in the standardization of quantitative RT-PCR reporting using the International Scale.