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| Status |
Public on Apr 23, 2024 |
| Title |
Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia [RNA-seq 2] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia, that is generally driven by PML-RARA, resulting from a balanced chromosomal translocation t(15;17) (q24.1;q21.2). However, approximately 2% of APL patients carry other variants of RARA-fusions, which pose challenges for diagnosis and treatment. Here, we report a novel t(14;17) translocation in an APL patient that gave rise to a new fusion gene, STRN3-RARA. STRN3 forms a complex called the striatin-interacting phosphatase and kinase (STRIPAK), which couples kinases to protein phosphatase 2A and regulates their activities. Like other APL patients with RARA-variants, this patient quickly relapsed after the initial response to all-trans retinoic acid (ATRA) treatment. Mechanistically, we demonstrated that STRN3-RARA, in cooperating with UTX deficiency, which was mutated in the patient, drove APL formation in mice. Additionally, we found that STRN3-RARA cells were specifically susceptible to the TNFα pathway. Inhibition of this pathway by cepharanthine, an FDA-approved drug, effectively suppressed the growth of U937 cells with STRN3-RARA expression, as well as relapsed APL cells from the patient. Taken together, our study identified a new APL fusion gene, STRN3-RARA, and validated it as a functional APL driver, providing insight into the diagnosis and treatment of non-classic APL patients.
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| Overall design |
Bulk RNAseq of murine sgUtx;SR APL cells treated with 200nM ATRA or vehicle in vitro. Bulk RNAseq of APL patient's bone marrow (BM) cells with STRN3-RARA(SR) fusion before treatment and treatment relapse.
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| Web link |
https://ashpublications.org/blood/article-abstract/142/17/1494/497635/Identifying-STRN3-RARA-as-a-new-fusion-gene-for?redirectedFrom=fulltext
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| Contributor(s) |
Chen X, Zhang Q, Chen C, Liu Y |
| Citation(s) |
37624915 |
| |
| Submission date |
Jul 26, 2023 |
| Last update date |
Apr 23, 2024 |
| Contact name |
Xaingyu Pan |
| E-mail(s) |
pangxueyu233@outlook.com
|
| Organization name |
Sichuan University
|
| Department |
State Key Laboratory of Biotherapy, West China Hospital, Sihcuan University.
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| Lab |
Chen & Liu Lab
|
| Street address |
No.17 Renming road section3
|
| City |
Chengdu, Cihna |
| State/province |
Sichuan |
| ZIP/Postal code |
610041 |
| Country |
China |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE224816 |
Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia |
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| Relations |
| BioProject |
PRJNA998875 |
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