Single-cell analysis of AIMP2 splice variants informs on drug sensitivity and prognosis in hematologic cancer

Jayoung Ku, Ryul Kim, Dongchan Kim, Daeyoon Kim, Seulki Song, Keonyong Lee, Namseok Lee, Min A. Kim, Sung Soo Yoon, Nam Hoon Kwon, Sunghoon Kim, Yoosik Kim, Youngil Koh

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon 2 skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises AIMP2 activity and is associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio is strongly correlated with major cancer signaling pathways and poor prognosis, particularly in acute myeloid leukemia (AML). Analysis of a clinical patient cohort revealed that AIMP2-DX2 positive AML patients show decreased overall survival and progression-free survival. We also developed targeted RNA-sequencing and single-molecule RNA-FISH tools to quantitatively analyze AIMP2-DX2/AIMP2 ratios at the single-cell level. By subclassifying hematologic cancer cells based on their AIMP2-DX2/AIMP2 ratios, we found that downregulating AIMP2-DX2 sensitizes cells to anticancer drugs only for a subgroup of cells while it has adverse effects on others. Collectively, our study establishes AIMP2-DX2 as a potential biomarker and a therapeutic target for hematologic cancer.

Original languageEnglish
Article number630
JournalCommunications Biology
Volume3
Issue number1
DOIs
Publication statusPublished - 2020 Dec 1

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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