Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms

Peiwen Zhang, Na You, Yiyi Ding, Wenqi Zhu, Nan Wang, Yueqiao Xie, Wanling Huang, Qian Ren, Tiejun Qin, Rongfeng Fu, Lei Zhang (), Zhijian Xiao (), Tao Cheng () and Xiaotong Ma ()
Additional contact information
Peiwen Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Na You: Chinese Academy of Medical Sciences & Peking Union Medical College
Yiyi Ding: Chinese Academy of Medical Sciences & Peking Union Medical College
Wenqi Zhu: Chinese Academy of Medical Sciences & Peking Union Medical College
Nan Wang: Chinese Academy of Medical Sciences & Peking Union Medical College
Yueqiao Xie: Chinese Academy of Medical Sciences & Peking Union Medical College
Wanling Huang: Chinese Academy of Medical Sciences & Peking Union Medical College
Qian Ren: Chinese Academy of Medical Sciences & Peking Union Medical College
Tiejun Qin: Chinese Academy of Medical Sciences & Peking Union Medical College
Rongfeng Fu: Chinese Academy of Medical Sciences & Peking Union Medical College
Lei Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Zhijian Xiao: Chinese Academy of Medical Sciences & Peking Union Medical College
Tao Cheng: Chinese Academy of Medical Sciences & Peking Union Medical College
Xiaotong Ma: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Despite the identification of driver mutations leading to the initiation of myeloproliferative neoplasms (MPNs), the molecular pathogenesis of MPNs remains incompletely understood. Here, we demonstrate that growth arrest and DNA damage inducible gamma (GADD45g) is expressed at significantly lower levels in patients with MPNs, and JAK2V617F mutation and histone deacetylation contribute to its reduced expression. Downregulation of GADD45g plays a tumor-promoting role in human MPN cells. Gadd45g insufficiency in the murine hematopoietic system alone leads to significantly enhanced growth and self-renewal capacity of myeloid-biased hematopoietic stem cells, and the development of phenotypes resembling MPNs. Mechanistically, the pathogenic role of GADD45g insufficiency is mediated through a cascade of activations of RAC2, PAK1 and PI3K-AKT signaling pathways. These data characterize GADD45g deficiency as a novel pathogenic factor in MPNs.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47297-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47297-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47297-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().