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Updated: Dec 3, 2025
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Single-cell analysis of AIMP2 splice variants informs on drug sensitivity and prognosis in hematologic cancer
Jayoung Ku1, Ryul Kim2, Dongchan Kim2
1Department of Chemical and Biomolecular Engineering and KAIST Institute for Health Science and Technology (KIHST), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
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.
Insights
The AIMP2-DX2 variant is linked to poor prognosis in acute myeloid leukemia (AML). Targeting this variant shows potential as a therapeutic strategy for hematologic cancers.
Area of Science:
- Molecular biology
- Cancer research
- Hematology
Background:
- Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is crucial for the multi-tRNA synthetase complex.
- The alternatively spliced variant AIMP2-DX2 disrupts AIMP2 function and is implicated in carcinogenesis.
- The clinical significance of AIMP2-DX2 in cancer, especially acute myeloid leukemia (AML), requires further investigation.
Purpose of the Study:
- To investigate the clinical relevance of the AIMP2-DX2/AIMP2 expression ratio in hematologic cancers.
- To develop quantitative methods for analyzing AIMP2-DX2/AIMP2 ratios at the single-cell level.
- To explore the therapeutic potential of targeting AIMP2-DX2 in hematologic malignancies.
Main Methods:
- Analysis of AIMP2-DX2/AIMP2 expression ratios in a clinical patient cohort.
- Development of targeted RNA-sequencing and single-molecule RNA-FISH for quantitative single-cell analysis.
- Subclassification of hematologic cancer cells based on AIMP2-DX2/AIMP2 ratios and assessment of drug sensitivity.
Main Results:
- A high AIMP2-DX2/AIMP2 ratio strongly correlates with major cancer signaling pathways and poor prognosis in AML.
- AIMP2-DX2 positive AML patients exhibit reduced overall survival and progression-free survival.
- Downregulating AIMP2-DX2 has differential effects on drug sensitivity across distinct cancer cell subgroups.
Conclusions:
- The AIMP2-DX2/AIMP2 expression ratio serves as a potential prognostic biomarker in AML.
- AIMP2-DX2 represents a potential therapeutic target for hematologic cancers.
- Single-cell based stratification by AIMP2-DX2/AIMP2 ratio is crucial for predicting treatment response.
