An Isoform-Specific RUNX1C–BTG2 Axis Governs AML Quiescence and Chemoresistance Article Swipe
Cuijuan Han
,
Zhiping Zhang
,
Edie I. Crosse
,
Sogand Sajedi
,
Bin Lü
,
Xiyue Wang
,
Sadik Karma
,
Mitch Kostich
,
Sakthi H. Rajendran
,
Dylan B. Udy
,
Steven Chen
,
Alexander Calderon
,
Abimbola Eunice. Lawal
,
Kathleen Koenig
,
Marshall McKenna
,
Patrick K. Reville
,
Hussein A. Abbas
,
Omar Abdel‐Wahab
,
Pedro Miura
,
Robert K. Bradley
,
Eric Wang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/2643-3230.bcd-24-0327
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/2643-3230.bcd-24-0327
Aberrant levels or structures of RNA isoforms are a hallmark of many cancers, including acute myeloid leukemia (AML), yet their role in AML chemoresistance remains unclear. We conducted a paired analysis of RNA isoform changes in patients with AML before therapy and at relapse after chemotherapy and identified intragenic DNA methylation at the proximal promoter of the transcription factor RUNX1, which resulted in elevated expression of the long-isoform RUNX1C through its alternative distal promoter. The unique N-terminal region of RUNX1C orchestrated an isoform-specific transcriptional program that promoted chemoresistance, with its direct target BTG2 playing a role in chemotherapy resistance. BTG2 promoted rRNA deadenylation, resulting in decreased mRNA expression and stability. Deletion of rRNAs increased cellular quiescence. Moreover, RNA-based targeting of RUNX1C reactivated quiescent leukemia cells and enhanced chemotherapy efficacy. These findings delineated an isoform-specific transcriptional circuit that governed chemotherapy response, providing a potential therapeutic strategy to mitigate AML recurrence. Significance: This study identifies RUNX1C as a contributor to AML chemoresistance and an inducer of quiescence through BTG2. Targeting RUNX1C with RNA-based approaches disrupts this state and improves chemotherapy response, highlighting RUNX1C inhibition as a promising strategy to overcome resistance and enhance treatment efficacy in AML.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1158/2643-3230.bcd-24-0327
- https://aacrjournals.org/bloodcancerdiscov/article-pdf/doi/10.1158/2643-3230.BCD-24-0327/3629892/bcd-24-0327.pdf
- OA Status
- hybrid
- Cited By
- 1
- References
- 85
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412119851
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4412119851Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/2643-3230.bcd-24-0327Digital Object Identifier
- Title
-
An Isoform-Specific RUNX1C–BTG2 Axis Governs AML Quiescence and ChemoresistanceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-07-09Full publication date if available
- Authors
-
Cuijuan Han, Zhiping Zhang, Edie I. Crosse, Sogand Sajedi, Bin Lü, Xiyue Wang, Sadik Karma, Mitch Kostich, Sakthi H. Rajendran, Dylan B. Udy, Steven Chen, Alexander Calderon, Abimbola Eunice. Lawal, Kathleen Koenig, Marshall McKenna, Patrick K. Reville, Hussein A. Abbas, Omar Abdel‐Wahab, Pedro Miura, Robert K. Bradley, Eric WangList of authors in order
- Landing page
-
https://doi.org/10.1158/2643-3230.bcd-24-0327Publisher landing page
- PDF URL
-
https://aacrjournals.org/bloodcancerdiscov/article-pdf/doi/10.1158/2643-3230.BCD-24-0327/3629892/bcd-24-0327.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://aacrjournals.org/bloodcancerdiscov/article-pdf/doi/10.1158/2643-3230.BCD-24-0327/3629892/bcd-24-0327.pdfDirect OA link when available
- Concepts
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Gene isoform, Cancer research, Biology, Myeloid leukemia, RNA, Transcription factor, Transcription (linguistics), Messenger RNA, Promoter, Chemotherapy, Molecular biology, Gene expression, Gene, Genetics, Philosophy, LinguisticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
- References (count)
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85Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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