The authors describe recurrent novel insertion/deletion mutations in the JH2 domain of JAK2 occurring in patients with eosinophilia as a prominent feature of their myeloproliferative neoplasms. Remarkably, 2 of the patients with a specific mutation (Leu583-Ala586DelInsSer) meet the criteria for both chronic eosinophilic leukemia and polycythemia vera, suggesting that this may be a distinct overlap syndrome.
Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.
Summary
Measurement of BCR activator of RhoGEF and GTPase ‐ABL proto‐oncogene 1, non‐receptor tyrosine kinase (BCR‐ABL1) mRNA levels by reverse transcription quantitative polymerase chain reaction (RTqPCR) has been critical to treatment protocols and clinical trials in chronic myeloid leukaemia; however, interlaboratory variation remains a significant issue. Reverse transcriptase droplet digital PCR (RTddPCR) has shown potential to improve testing but a large‐scale interlaboratory study is required to definitively establish this. In the present study, 10 BCR‐ABL1‐positive samples with levels ranging from molecular response (MR)1·0–MR5·0 were tested by 23 laboratories using RTddPCR with the QXDX BCR‐ABL %IS kit. A subset of participants tested the samples using RTqPCR. All 23 participants using RTddPCR detected BCR‐ABL1 in all samples to MR4·0. Detection rates for deep‐response samples were 95·7% at MR4·5, 78·3% at MR4·7 and 87·0% at MR5·0. Interlaboratory coefficient of variation was indirectly proportional to BCR‐ABL1 level ranging from 29·3% to 69·0%. Linearity ranged from 0·9330 to 1·000 (average 0·9936). When results were compared for the 11 participants who performed both RTddPCR and RTqPCR, RTddPCR showed a similar limit of detection to RTqPCR with reduced interlaboratory variation and better assay linearity. The ability to detect deep responses with RTddPCR, matched with an improved linearity and reduced interlaboratory variation will allow improved patient management, and is of particular importance for future clinical trials focussed on achieving and maintaining treatment‐free remission.
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