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Differentially expressed genes were identified using the GSE112278 dataset, followed by weighted gene co-expression network analysis (WGCNA) to screen hub genes. Single-cell RNA-seq data from GSE196676 were analyzed using the Seurat package to assess immune cell composition, gene expression, and cell\u2013cell communication. CDKN1A expression was experimentally modulated in RAW264.7 macrophages via siRNA knockdown or plasmid overexpression. Phagocytic function was assessed using CFDA-labeled mouse platelets and F4\/80 immunofluorescence staining. Molecular docking was conducted to evaluate the interaction between Eltrombopag and CDKN1A. Through intersection analysis, we identified CDKN1A as a key gene influencing the response of ITP patients to Eltrombopag treatment. Single-cell data analysis revealed a significant increase in the proportion of macrophages in ITP patients, accompanied by downregulation of CDKN1A expression in these macrophages, which was closely associated with macrophage activation and enhanced phagocytic capacity. Functional experiments confirmed that CDKN1A knockdown promoted, while overexpression inhibited, macrophage phagocytosis of platelets. Additionally, cell communication analysis demonstrated that macrophages in ITP patients interact with transitional B cells via the TGF\u03b2 signaling pathway. Further analysis revealed that a subset of macrophages performs effector functions by differentiating into specialized subtypes that function independently, without direct interaction with other immune cells. Our study identified CDKN1A as a key regulator of Eltrombopag\u2019s effectiveness in treating ITP. CDKN1A expression was reduced in macrophages of ITP patients and that it interacted with transitional B cells through the TGF\u03b2 signaling pathway to promote disease progression. These findings offer new insights into the pathogenic mechanisms of ITP and suggest CDKN1A as a potential therapeutic target for future interventions.<\/jats:p>","DOI":"10.1007\/s00277-025-06436-5","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T03:19:19Z","timestamp":1749871159000},"page":"3183-3197","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CDKN1A as a potential target for Eltrombopag treatment in ITP and its regulation of the communication between macrophages and transitional B cells in ITP"],"prefix":"10.1007","volume":"104","author":[{"given":"Shixuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mankai","family":"Ju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fancong","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yechao","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiming","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genmei","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"issue":"23","key":"6436_CR1","doi-asserted-by":"publisher","first-page":"3829","DOI":"10.1182\/bloodadvances.2019000966","volume":"3","author":"C Neunert","year":"2019","unstructured":"Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N et al (2019) American society of hematology 2019 guidelines for immune thrombocytopenia. 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