{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T17:50:45Z","timestamp":1743011445342},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,6,13]],"date-time":"2012-06-13T00:00:00Z","timestamp":1339545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>P\u00fclhorn H, Herrmann M, Harms H, Jung A &amp; Baumann I \u2028(2012) <jats:italic>Histopathology<\/jats:italic>\u00a0<jats:bold>61,<\/jats:bold> 200\u2013211<\/jats:p><jats:p><jats:bold>Apoptotic cells and clonally expanded cytotoxic T cells in bone marrow trephines of patients with myelodysplastic syndrome<\/jats:bold><\/jats:p><jats:p><jats:bold>Aims:\u2002<\/jats:bold> There is increasing evidence that autoimmunity is involved in the pathogenesis of myelodysplastic syndromes (MDS). We examined the number of apoptotic cells, and analysed the T cells and the T cell receptor gene rearrangements in bone marrow trephines of patients with low\u2010grade MDS [refractory anaemia (RA), refractory anaemia with ringed sideroblasts (RAS) and refractory cytopenia with multilineage dysplasia (RCMD)] to investigate the correlation between T cells and apoptosis.<\/jats:p><jats:p><jats:bold>Methods and results:\u2002<\/jats:bold> Bone marrow trephines from 30 patients with RA, seven patients with RCMD, four patients with RAS and 11 normal bone marrow donors were stained for CD3 and for apoptotic cells using immunohistochemistry and terminal deoxynucleotidyl transferase 2\u2032\u2010deoxyuridine, 5\u2032\u2010triphosphate (dUTP) nick end labelling (TUNEL) technique, respectively. The positive cells were quantified by computer\u2010assisted image analysis. In addition, CD 8 and T cell\u2010restricted intracellular antigen\u20101 (TIA\u20101)\u2010positive cells were analysed by single staining and evaluated semiquantitatively by light microscopy. Junctional diversity of the T cell receptor (TCR) \u03b1\u2010, \u03b2\u2010 and \u03b3\u2010chains were analysed in 24 cases of RA and RCMD by reverse transcription\u2013polymerase chain reaction (RT\u2013PCR). In all cases of RA, RCMD and RAS an increase of apoptotic cells was accompanied by an increase of T cells, when compared to normal donors (<jats:italic>P\u2003<\/jats:italic>&lt;<jats:italic>\u2003<\/jats:italic>0.001). Expression of TIA\u20101 was found in 33 of 41 patients with low\u2010grade MDS. In contrast, normal controls showed either no or only very weak expression. Furthermore, 14 of 24 cases with low\u2010grade MDS showed clonal TCR gene rearrangement.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> These findings provide evidence that increased apoptosis in low\u2010grade MDS correlates with increased numbers of cytotoxic T cells. A considerable proportion of the MDS cases showed clonal TCR rearrangement suggesting an antigen\u2010driven selection of the T cells. We therefore speculate that cases of MDS can be accompanied by a presumably autoreactive T cell\u2010mediated apoptosis induction in bone marrow cells.<\/jats:p>","DOI":"10.1111\/j.1365-2559.2012.04209.x","type":"journal-article","created":{"date-parts":[[2012,6,13]],"date-time":"2012-06-13T08:51:45Z","timestamp":1339577505000},"page":"200-211","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Apoptotic cells and clonally expanded cytotoxic T cells in bone marrow trephines of patients with myelodysplastic syndrome"],"prefix":"10.1111","volume":"61","author":[{"given":"Heinke","family":"P\u00fclhorn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry","family":"Harms","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irith","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198708203170802"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.05.005"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1594"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(98)00112-X"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400980"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.1.268.bloodjournal861268"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830490204"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-005-1034-4"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(94)00134-V"},{"key":"e_1_2_6_11_2","first-page":"42","article-title":"High incidence of apoptosis in peripheral blood of myelodysplastic syndrome patients determined by Papanicolaou\u2010stained preparations","volume":"9","author":"Emura I","year":"2003","journal-title":"Lab. 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