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Editorials
inflammatory clinical features in MDS patients. TET2 and splice gene mutations, common in MDS, contribute to inflammatory gene expression in macrophages and are associated with cardiovascular inflammatory comorbidi- ties. Acute leukemic transformation is more frequent in MDS patients with autoinflammatory features than in those without. Recently, a clinically severe autoinflam- matory disease associated with MDS and other myeloid disorders termed VEXAS syndrome (characterized by Vacuoles in myeloid precursors, E1-ubiquitinating enzyme abnormal function, X-linked, Autoinflammatory disorders, Somatic mutation) has been ascribed to a somatic mutation in the UBA1 gene.15 This disorder has escaped much prior clinical attention since the gene is not captured by most current next-generation sequencing mutation panels.
Treatment of MDS patients wih disordered immuno- logical and inflammatory components has been problem- atic. For certain associated diseases, such as CAPS and Schnitzler syndrome with NLRP3 activation, IL-1 and IL- 1 receptor antagonists have been beneficial in disease management and are now being considered for MDS.11,12,16 Although some MDS patients with both disease elements may respond to therapy with hypomethylating agents or to antagonists of IL-1 or IL-6 or their respective receptors, these drugs appear to have only temporizing effects in this disease setting; nevertheless, they may be steroid- sparing as an aid to symptom management.17 Other molecular targets have been evaluated for the treatment of such patients, including inhibition of the Toll receptor or Bruton tyrosine kinase signaling.2 The more recently discovered NEK7 component of NLRP3 activation may provide a novel target for inhibitors of the inflamma- some’s upstream effector arm.12 In addition, given the important role of T in controlling inflammation and of
tion of Treg usage as a feature of cellular therapeutic approaches for such patients may prove valuable in this neoplastic disease with disordered innate immunity.18
Thus, the paper by Wang et al.13 heralds methods to improve understanding of pathogenic mechanisms under- lying critical interactions between inflammation and myeloid neoplasia. Such advances should facilitate the development of more effective approaches to the treat- ment of the dysplastic innate immunity involved in the hemato-inflammatory nature of MDS.
Disclosures
No conflicts of interest to disclose.
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