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Primary CD34 + cells of patients with vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic (VEXAS) syndrome are highly sensitive to targeted treatment with TAK‐243

Year: 2025

Type: article

Abstract: TAK-243 selectively targets UBA1-mutated VEXAS CD34 + cells.Non-expanded (black dots) and expanded (circles) CD34 + cells of patients VEXAS1, VEXAS4 and VEXAS5 were treated with the IC25, IC50 and IC75 values of TAK-243 (A) or pevonedistat (B) for 48 h.The cells were then harvested for DNA isolation.(A, B) The variant allele frequency (VAF) of UBA1 for each condition was determined by droplet digital PCR (ddPCR).Vehicle control was set to 100% and the other values were normalized accordingly.(C, D) Based on the UBA1 VAFs determined by ddPCR, the proportion of UBA1-mutated and non-mutated cells was determined.The raw data of the ddPCR results can be found in Table S3.Data were analysed using ordinary one-way (A, B) or two-way (C, D) analysis of variance (anova) using Prism 10 (GraphPad Software), and are represented as mean ± SD. ns, not significant, *p ≤ 0.05.VEXAS, vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic.

Source: British Journal of Haematology

DOI: 10.1111/bjh.70203