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Updated: Jul 14, 2026
10:25
Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
DHX15 affects AML1-ETO9a splicing together with HNRNPL, RBM33 in AML1-ETO-positive acute myeloid leukaemia
Qiao Liu1,2, Xuechun Wang1,2, Jiqiang Fan3
1Fujian Provincial Key Laboratory on Hematology, Department of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
British Journal of Haematology
|July 13, 2026
Summary
RNA helicase DHX15 is involved in acute myeloid leukemia (AML) progression by promoting the oncogenic AML1-ETO9a (AE9a) splice variant. DHX15, HNRNPL, and RBM33 contribute to AE9a splicing and leukemogenesis in AE-positive AML.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- The AML1-ETO (AE) fusion gene is a prevalent driver in acute myeloid leukemia (AML).
- The oncogenic AML1-ETO9a (AE9a) splice variant arises from aberrant splicing of the ETO gene.
- Understanding the regulatory mechanisms of AE9a splicing is crucial for AML treatment.
Purpose of the Study:
- To investigate the role of RNA helicase DHX15 in AE9a splicing and AML progression.
- To identify other regulatory factors involved in AE9a splicing.
- To explore the therapeutic potential of targeting DHX15 in AE-positive AML.
Main Methods:
- Quantitative analysis of DHX15, AE, and AE9a expression in AML patient samples.
- In vitro knockdown of DHX15 in AML cell lines.
- In vivo studies using AE-positive leukemia mouse models.
- RNA immunoprecipitation and RNA pull-down assays to identify interacting proteins.
- 3D structure prediction of regulatory complexes.
Main Results:
- Higher DHX15 expression correlates with increased AE9a/AE abundance and poor prognosis in AE-positive AML patients.
- DHX15 knockdown inhibits cell proliferation, induces cell cycle arrest, and prolongs survival in vivo.
- DHX15 directly binds to AE and AE9a transcripts.
- HNRNPL and RBM33 selectively interact with AE9a transcripts and are essential for AE9a expression.
- DHX15, HNRNPL, and RBM33 form a regulatory complex involved in AE9a splicing.
Conclusions:
- DHX15 plays a critical role in AE9a splicing and contributes to leukemogenesis in AE-positive AML.
- DHX15, HNRNPL, and RBM33 form a complex that regulates AE9a splicing.
- Targeting DHX15, HNRNPL, or RBM33 may offer novel therapeutic strategies for AE-positive AML.
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