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. 2025 Feb;206(2):758-762.
doi: 10.1111/bjh.19979. Epub 2025 Jan 15.

JAK2 is a critical therapeutic target in VEXAS syndrome treated with ruxolitinib

Andrea Ceccardi  1   2 , Martina Dameri  2 , Francesco Ravera  1   2 , Nicolò Gilardi  1   2 , Mario Stabile  1   2   3 , Isabella Lombardo  4 , Davide Ceresa  2 , Monica Colombo  5 , Tiziana Vigo  6 , Benedetta Cigolini  1   2 , Giulia Rivoli  7 , Matteo Dragani  7 , Irene Solimano  1 , Anna Garuti  2 , Andrea Bellodi  2 , Alberto Ballestrero  1   2 , Lorenzo Ferrando  2 , Gabriele Zoppoli  1   2
Affiliations

JAK2 is a critical therapeutic target in VEXAS syndrome treated with ruxolitinib

Andrea Ceccardi et al. Br J Haematol. 2025 Feb.
No abstract available

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Conflict of interest statement

GZ declares consultancy fees from Menarini Stemline and holds the co‐ownership of Immunomica Ltd. The remaining authors have no conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Blood transcriptional response to treatment with ruxolitinib in VEXAS syndrome. (A) Diagram summarizing the patient's clinical course and sample collection timeline. (B) Blood transcriptional response of the VEXAS signature from day 0 to day 11 of treatment with ruxolitinib. Y axis represents percentage change, normalized by its maximum and minimum value, over time. (C) Polar bar plot highlighting the correlations between VEXAS signature and standard laboratory parameters through Pearson's correlation coefficients, with positive correlations displayed in shades of red and negative correlations in blue. (D) Dynamics of blood transcripts of JAK1 and JAK2 during ruxolitinib treatment. Transcripts are expressed in counts per million (CPM). Y axis represents percentage change compared to transcript baseline. (E) Correlation matrix depicting associations among VEXAS, interferon, and plasma cell signatures and transcripts of the genes JAK1 and JAK2. Positive correlations are displayed in red, while negative correlations are depicted in blue. Pearson's correlation coefficients are reported within each square. Ba, Basophils; CPR, C‐reactive protein; D, day; Eo, eosinophils; Hb, haemoglobin; Hct, haematocrit; IFN, interferon; JAK, janus kinase; L, lymphocytes; LAD, lactate dehydrogenase; MCH, mean corpuscular haemoglobin; MCHC, mean corpuscular haemoglobin concentration, MCV, mean corpuscular volume; Mo, monocytes; MPV, mean platelet volume; N, neutrophils; PCs, plasma cells; PLTs, platelets; RBCs, red blood cells; RDW, red cell distribution width; VEXAS, vacuoles, E1 enzyme, X‐linked, autoinflammatory and somatic; WBCs, white blood cells.
FIGURE 2
FIGURE 2
Transcriptional response to ruxolitinib in VEXAS skin lesions. (A) Transcriptional response of the VEXAS and interferon signatures and JAK1 and JAK2 transcripts in VEXAS skin lesions before and after ruxolitinib initiation. Signature enrichment and transcript expression have been separately scaled and are displayed in terms of Z score. (B) Immune cell deconvolution of bulk RNA‐seq of VEXAS skin lesions before and after ruxolitinib initiation. Y axis represents the percentage of the different immune cell types on day 0 and day 5. (C) UMAP depicting scRNA‐seq clusters (left panel) of a VEXAS skin lesion after ruxolitinib initiation, with a focus on JAK1 (middle panel) and JAK2 (right panel) transcripts. Clusters were generated using the Seurat and Leidenalg packages, and automatically annotated with the CellTypist tool. Annotated clusters were further reviewed manually. JAK, janus kinase; VEXAS, vacuoles, E1 enzyme, X‐linked, autoinflammatory and somatic.
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