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. 2025 Mar 25;9(6):1261-1266.
doi: 10.1182/bloodadvances.2024014387.

Combination therapies of porcupine inhibition with ruxolitinib, ibrutinib, or belumosudil in murine sclerodermatous GVHD

Xuezhi Hong  1   2   3   4 , Yanhua Xiao  1   2   3   4 , Liyan Xu  1   2   3   4 , Lichong Shen  3   4 , Ranjana Neelagar  1   2 , Veda Devakumar  1   2 , Thuong Trinh-Minh  1   2 , Minrui Liang  1   2 , Aleix Rius Rigau  3   4 , Yun Zhang  1   2 , Yi-Nan Li  1   2 , Clara Dees  3   4 , Andrea-Hermina Györfi  1   2   5 , Daniel Wolff  6 , Wolfgang Herr  6 , Georg Schett  3   4 , Jörg H W Distler  1   2   5 , Alexandru-Emil Matei  1   2   5
Affiliations

Combination therapies of porcupine inhibition with ruxolitinib, ibrutinib, or belumosudil in murine sclerodermatous GVHD

Xuezhi Hong et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: J.H.W.D. has acted as a consultant for Actelion, Active Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, JB Therapeutics, Medac, Pfizer, Ruiyi, and Union Chimique Belge; has received research funding from Anamar, Active Biotech, Array Biopharma, aTyr Pharma, Bristol Myers Squibb, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, Novartis, Sanofi-Aventis, RedX, and Union Chimique Belge; and owns stock in 4D Science. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Signaling pathways targeted by Wnt-C59, ruxolitinib, ibrutinib, or belumosudil are enriched in both human and murine sclGVHD. (A-B) RNA-seq data were analyzed from 6 patients with sclGVHD and 6 healthy controls (A) as well as from 4 allogeneic (sclGVHD model, vehicle-treated) and 4 syngeneic mice (B). Bubble plots illustrating selected significantly enriched biological processes from Gene Ontology (GO) pathway analysis. The color of each bubble represents the adjusted P value (Padj), whereas the size of the bubble represents the number of differentially expressed genes associated with the respective GO processes. On the left side are marked the signaling pathways directly targeted by Wnt-C59, ruxolitinib, ibrutinib, or belumosudil (WNT–Wnt-C59, BTK–ibrutinib, ROCK–belumosudil, and JAK–ruxolitinib), corresponding to the respective GO processes on the right side. APC, antigen-presenting cell; GTP, guanosine triphosphate.
Figure 2.
Figure 2.
Wnt-C59 in monotherapy or in combination with ruxolitinib, ibrutinib, or belumosudil ameliorates skin fibrosis in sclGVHD. (A) Representative trichrome staining of the skin of sclGVHD mice at 100-fold magnification (scale bars = 250 μm). The skin thickness is indicated by a vertical line. Quantification of dermal thickening, hydroxyproline content, and number of myofibroblasts in the dermis after monotherapy (B), or Wnt-C59 in combination with belumosudil (C). Data are represented as mean ± standard deviation of n = 7 to 8 independent biological samples per group. P values were determined by 1-way analysis of variance with the Newman-Keuls test. ∗.05 > P > .01; ∗∗.01 > P > .001; ∗∗∗P < .001. HP, hydroxyproline; ns, not significant.
See this image and copyright information in PMC

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