Abstract
MPL exon 10 mutations are one of the driver mutations in essential thrombocythemia (ET) or myelofibrosis (MF). We have established an in-house MPL mutation analysis system, covering the entire region of MPL exon 10 by direct sequencing. Since 2009, MPL exon 10 mutation analysis has been performed for diagnosis of myeloproliferative neoplasms (MPN) without JAK2 V617F or CALR exon 9 mutations. So far, 11 cases of MPL exon 10 mutation have been found in 51 patients with suspected MPN. In patients with ET, we detected five non-canonical MPL mutations including one novel mutation, MPL R514_P518delinsK, and one canonical MPL W515L mutation. Notably, three ET patients without canonical MPL mutations had thrombotic events. Meanwhile, in primary or secondary MF, only canonical MPL W515L/K mutations were found. Further cases need to be examined to elucidate the full MPL mutation profile in MPN. However, our data indicate that analysis of the whole of MPL exon 10 is warranted for the diagnosis of MPL mutations, especially in ET, and that the use of Japanese commercial laboratory tests that only detect canonical MPL W515L/K mutations may miss a significant percentage of MPL exon 10 mutations, which could delay the administration of anti-thrombotic therapy.
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Acknowledgements
We thank Catherine Perfect, MA (Cantab), from Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript.
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Y. Sugimoto has received honoraria from Novartis and is an accepted researcher from Shojunkai Takeuchi Hospital. Y. Sugimoto and I. Tawara received funding from Takara Bio. Y. Sugimoto, K. Nagaharu, K. Ohishi, I. Tawara, and N. Katayama have received research support from Astellas, Kyowa Kirin, and Ono. K. Ohishi has received funding from PharmaEssentia. N. Katayama has received honoraria from Novartis, Celgene, and Chugai. No other authors have any conflicts of interest to declare.
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Sugimoto, Y., Nagaharu, K., Ohishi, K. et al. MPL exon 10 mutations other than canonical MPL W515L/K mutations identified by in-house MPL exon 10 direct sequencing in essential thrombocythemia. Int J Hematol 113, 618–621 (2021). https://doi.org/10.1007/s12185-021-03134-6
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DOI: https://doi.org/10.1007/s12185-021-03134-6