論文

国際誌
2022年8月26日

Exploring the mechanistic link between SF3B1 mutation and ring sideroblast formation in myelodysplastic syndrome.

Scientific reports
  • Tetsuro Ochi
  • Tohru Fujiwara
  • Koya Ono
  • Chie Suzuki
  • Maika Nikaido
  • Daichi Inoue
  • Hiroki Kato
  • Koichi Onodera
  • Satoshi Ichikawa
  • Noriko Fukuhara
  • Yasushi Onishi
  • Hisayuki Yokoyama
  • Yukio Nakamura
  • Hideo Harigae
  • 全て表示

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1
開始ページ
14562
終了ページ
14562
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-022-18921-2

Acquired sideroblastic anemia, characterized by bone marrow ring sideroblasts (RS), is predominantly associated with myelodysplastic syndrome (MDS). Although somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery, are frequently found in MDS-RS, the detailed mechanism contributing to RS formation is unknown. To explore the mechanism, we established human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells stably expressing SF3B1K700E. SF3B1K700E expressing cells showed higher proportion of RS than the control cells along with erythroid differentiation, indicating the direct contribution of mutant SF3B1 expression in erythroblasts to RS formation. In SF3B1K700E expressing cells, ABCB7 and ALAS2, known causative genes for congenital sideroblastic anemia, were downregulated. Additionally, mis-splicing of ABCB7 was observed in SF3B1K700E expressing cells. ABCB7-knockdown HUDEP-2 cells revealed an increased frequency of RS formation along with erythroid differentiation, demonstrating the direct molecular link between ABCB7 defects and RS formation. ALAS2 protein levels were obviously decreased in ABCB7-knockdown cells, indicating decreased ALAS2 translation owing to impaired Fe-S cluster export by ABCB7 defects. Finally, RNA-seq analysis of MDS clinical samples demonstrated decreased expression of ABCB7 by the SF3B1 mutation. Our findings contribute to the elucidation of the complex mechanisms of RS formation in MDS-RS.

リンク情報
DOI
https://doi.org/10.1038/s41598-022-18921-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/36028755
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9418223
ID情報
  • DOI : 10.1038/s41598-022-18921-2
  • PubMed ID : 36028755
  • PubMed Central 記事ID : PMC9418223

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