Mutation of ten-eleven translocation-2 is associated with increased risk of autoimmune disease in patients with myelodysplastic syndrome
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Background/Aims: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS. Methods: Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed. Results: The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation- 2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance. Conclusions: Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.
Abstract
Background/Aims: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS. Methods: Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed. Results: The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation- 2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance. Conclusions: Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.
참고문헌 (26)
- Glenthoj A, "Immune mechanisms in myelodysplastic syndrome", Int J Mol Sci, 17, pp.E944~ (2016)
- Yogarajah M, "Leukemic transformation in myeloproliferative neoplasms : a literature review on risk, characteristics, and outcome", Mayo Clin Proc, 92, pp.1118~1128 (2017)
- Giannouli S, "Autoimmune phenomena in myelodysplastic syndromes: a 4-yr prospective study", Rheumatology(Oxford), 43, pp.626~632 (2004)
- Lee SJ, "Certain autoimmune manifestations are associated with distinctive karyotypes and outcomes in patients with myelodysplastic syndrome:a retrospective cohort study", Medicine(Baltimore), 95, pp.e3091~ (2016)
- Ades L, "Myelodysplastic syndromes", Lancet, 383, pp.2239~2252 (2014)
- Vardiman JW, "The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes", Blood, 114, pp.937~951 (2009)
- Aletaha D, "2010 Rheumatoid arthritis classification criteria : an American College of Rheumatology", European League Against Rheumatism collaborative initiative, 2010, pp.62, 2569~2581
- van der Linden S, "Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria", Arthritis Rheum, 27, pp.361~368 (1984)
- Bohan A, "Polymyositis and dermatomyositis(first of two parts)", N Engl J Med, 292, pp.344~347 (1975)
- Mughal TI, "An International MDS", MPN Working Group’s perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic, Haematologica, pp.2015, 100[DOI]
- Papaemmanuil E, "Clinical and biological implications of driver mutations in myelodysplastic syndromes", Blood, 122, pp.3616~3627 (2013)
- Haferlach T, "Landscape of genetic lesions in 944 patients with myelodysplastic syndromes", Leukemia, 28, pp.241~247 (2014)
- Braun T, "Myelodysplastic syndromes (MDS)and autoimmune disorders (AD): cause or consequence?", Best Pract Res Clin Haematol, 26, pp.327~336 (2013)
- Cooper GS, "Recent insights in the epidemiology of autoimmune diseases : improved prevalence estimates and understanding of clustering of diseases", J Autoimmun, 33, pp.197~207 (2009)
- Komrokji RS, "Autoimmune diseases and myelodysplastic syndromes", Am J Hematol, 91, pp.E280~E283 (2016)
- Esatoglu SN, "A reappraisal of the association between Behçet’s disease, myelodysplastic syndrome and the presence of trisomy 8 : a systematic literature review", Clin Exp Rheumatol, 33(6 Suppl 94), pp.S145~S151 (2015)
- Giagounidis AA, "Autoimmune disorders in two patients with myelodysplastic syndrome and 5q deletion", Acta Haematol, 113, pp.146~149 (2005)
- Vainchenker W, "Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms", Blood, 129, pp.667~679 (2017)
- Solary E, "The ten-eleven translocation-2(TET2)gene in hematopoiesis and hematopoietic diseases", Leukemia, 28, pp.485~496 (2014)
- Ko M, "Ten-eleven-translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice", Proc Natl Acad Sci U S A, 108, pp.14566~14571 (2011)
- Ichiyama K, "The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells", Immunity, 42, pp.613~626 (2015)
- Fuster JJ, "Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice", Science, 355, pp.842~847 (2017)
- Langemeijer SM, "TET2 mutations in childhood leukemia", Leukemia, 25, pp.189~192 (2011)
- Metzeler KH, "TET2mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study", J Clin Oncol, 29, pp.1373~1381 (2011)
- Busque L, "Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis", Nat Genet, 44, pp.1179~1181 (2012)
- Mohan SV, "Giant cell arteritis: immune and vascular aging as disease risk factors", Arthritis Res Ther, 13, pp.231~ (2011)