A Novel Subtype of Myeloproliferative Neoplasms Driven by a MYC-Alarmin Axis Article Swipe
Nicole D. Vincelette
,
Xiaoqing Yu
,
Andrew Kuykendall
,
Jungwon Moon
,
Siyuan Su
,
Chia‐Ho Cheng
,
Rinzine Sammut
,
Tiffany N. Razabdouski
,
Hai V. Nguyen
,
Erika A. Eksioglu
,
Onyee Chan
,
Najla Al Ali
,
Parth Patel
,
Dae Hyun Lee
,
Shima Nakanishi
,
Renan B. Ferreira
,
Qianxing Mo
,
Suzanne Cory
,
Harshani R. Lawrence
,
Ling Zhang
,
Daniel J. Murphy
,
Rami S. Komrokji
,
Dae-Sung Lee
,
Scott H. Kaufmann
,
John L. Cleveland
,
Seongseok Yun
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.09.25.559138
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.09.25.559138
Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPNs) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for triple negative myelofibrosis (MF) patients whose MPNs lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in triple negative MF, and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves various hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs. SIGNIFICANCE This study establishes that MYC expression is increased in triple negative MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in triple negative MPN.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.09.25.559138
- https://www.biorxiv.org/content/biorxiv/early/2023/09/26/2023.09.25.559138.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 139
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4387044177
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4387044177Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2023.09.25.559138Digital Object Identifier
- Title
-
A Novel Subtype of Myeloproliferative Neoplasms Driven by a MYC-Alarmin AxisWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-09-26Full publication date if available
- Authors
-
Nicole D. Vincelette, Xiaoqing Yu, Andrew Kuykendall, Jungwon Moon, Siyuan Su, Chia‐Ho Cheng, Rinzine Sammut, Tiffany N. Razabdouski, Hai V. Nguyen, Erika A. Eksioglu, Onyee Chan, Najla Al Ali, Parth Patel, Dae Hyun Lee, Shima Nakanishi, Renan B. Ferreira, Qianxing Mo, Suzanne Cory, Harshani R. Lawrence, Ling Zhang, Daniel J. Murphy, Rami S. Komrokji, Dae-Sung Lee, Scott H. Kaufmann, John L. Cleveland, Seongseok YunList of authors in order
- Landing page
-
https://doi.org/10.1101/2023.09.25.559138Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2023/09/26/2023.09.25.559138.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2023/09/26/2023.09.25.559138.full.pdfDirect OA link when available
- Concepts
-
Cancer research, Myelofibrosis, Haematopoiesis, Biology, Inflammation, S100A9, PI3K/AKT/mTOR pathway, Myeloproliferative Disorders, Signal transduction, Bone marrow, Medicine, Immunology, Stem cell, Cell biologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 1Per-year citation counts (last 5 years)
- References (count)
-
139Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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