Hereditary thrombocythemia due to splicing donor site mutation of THPO in a Japanese family.

Hiroyuki Kimura, Masahiro Onozawa, Junichi Hashiguchi, Daisuke Hidaka, Minoru Kanaya, Toshihiro Matsukawa, Hiromi Okada, Takeshi Kondo, Yoshihiro Matsuno, Takanori Teshima

Annals of hematology 2024 Jan

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Thrombopoietin (THPO) is an essential factor for platelet production. Hereditary thrombocythemia (HT) is caused by a germline mutation of THPO, MPL, or JAK2 and is inherited in an autosomal-dominant manner. We identified a Japanese family with HT due to a point mutation of the splicing donor site of the THPO gene (THPO c.13 + 1G > A). Bone marrow biopsy showed increased megakaryocytes mimicking essential thrombocythemia. One affected family member developed chronic myeloid leukemia. We cloned the mutation and developed mutated and wild type THPO expression vectors. Molecular analysis showed that the mutation causes an exon 3 skipping transcript of THPO that abrogates a suppressive untranslated upstream open reading frame. Although the transcript levels of THPO mRNA were comparable, mutated transcripts were more efficiently translated and THPO protein expression was significantly higher than that of the wild type. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Hiroyuki Kimura, Masahiro Onozawa, Junichi Hashiguchi, Daisuke Hidaka, Minoru Kanaya, Toshihiro Matsukawa, Hiromi Okada, Takeshi Kondo, Yoshihiro Matsuno, Takanori Teshima. Hereditary thrombocythemia due to splicing donor site mutation of THPO in a Japanese family. Annals of hematology. 2024 Jan;103(1):89-96