title: The implications of myelodysplastic syndrome - associated chromosomal abnormalities in the development of graft-versus-host disease.
abstract: There is a growing body of evidences that acquired chromosomal abnormalities in bone marrow (BM) cells are associated with clinical manifestations of myelodysplastic syndrome (MDS). However, to our knowledge, there are no reports that describe the association between chromosomal abnormalities in MDS and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). Here, we describe two MDS cases with trisomy 8 and der(1;7)(q10;p10), who developed severe GVHD after allo-SCT. We analyzed cytokine production and cell survival of monocytes from these patients with MDS before allo-SCT, in comparison with healthy controls or an MDS patient with a different chromosomal abnormality, who has not developed GVHD. The monocytes from MDS patients with trisomy 8 and der(1;7)(q10;p10) produced a larger amount of pro-inflammatory cytokine, tumor necrosis factor-α, and a smaller amount of anti-inflammatory cytokine, interleukin-10, on stimulation with Toll-like receptor (TLR) ligands. In addition, the monocytes from MDS cases with GVHD showed a decrease in apoptotic cell death upon stimulation with TLR ligands. We also detected host-derived pro-inflammatory antigen-presenting cells (APCs) in skin GVHD lesions after allo-SCT. These data suggest that trisomy 8 and der(1;7)(q10;p10) may be associated with the development of severe GVHD, by prolonging survival of pro-inflammatory host-derived APCs in GVHD lesions.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arai
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamashita
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Mizugishi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D012871:Skin Diseases / Q000097:blood / Q000235:genetics*; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014314:Trisomy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10