Publication Date:
2020-11-05
Description:
Introduction: Approximately 20% of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are associated with SIAD, but pathophysiological mechanisms underlying this association remain largely unknown and data on somatic mutations are very scarce. Autoreactive T lymphocytes play a major role in SIAD development. The main objective of this study was to investigate the mutational landscape of MDS/CMML associated with SIAD, and its impact on the immunological phenotype of T lymphocytes. Patients and Methods: This retrospective study was conducted in the hematology department of Hôpital Saint-Louis, Paris, in all MDS/CMML patients diagnosed between 2012 and 2017, and with a molecular analysis by NGS targeting a panel of 80 genes. MDS/CMML patients with associated SIAD (n= 85, whose diagnosis was based on usual international criteria) were compared with MDS/CMML patients without SIAD (n=319) who constituted the control cohort. Flow cytometry was performed on peripheral blood samples from 28 MDS/CMML patients (of whom 12/28 had SIAD) and 18 healthy controls, on a BD Fortessa X20 to study CD8+T lymphocytes subsets and the expression of immune checkpoints. Analysis was performed with FlowAI R v1.14.0 and Cytobank website for T cells clustering with unsupervised Citrus algorithm. Results: We included 404 MDS/CMML patients (323 MDS, 81 CMML), of whom 85 (21%) had SIAD diagnoses including 35 (34%) inflammatory arthritis, 20 (19%) systemic vasculitis, 16 (15%) autoimmune cytopenias, 15 (14%) connective tissue diseases, 9 (9%) neutrophilic dermatosis, 6 (6%) inflammatory bowel disease, and 3 (3%) unclassified SIAD. Both SIAD and control cohorts were similar in terms of age, levels of cytopenias, MDS/CMML subtypes and cytogenetic features. There was a preponderance of low risk MDS/CMML (85.9% and 82.8% in SIAD and control cohort), and the number of patients with CMML did not differ between the 2 groups (p=0.36). Median follow-up was 32.2 months in the whole cohort. Median overall survival was 95.7 months [60.7 - not estimable] and 101.0 months [70.8 - not estimable] in the control and SIAD cohort respectively (p=0.91). Figure A represents the mutational landscape of MDS/CMML patients for the recurrent mutated genes. Median number of mutations was 2 [1-4] in both cohorts (ns). TET2mutations were found in 39/85 (46%) and 108/319 (34%) patients in the SIAD and control cohorts respectively (p=0.04), and IDH1/2 mutationsin 12/85 (14%) patients in the SIAD cohort vs 14/319 (4%) in the control group (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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