Graft-versus-host disease: role of inflammation in the development of chromosomal abnormalities of keratinocytes. Biol Blood Marrow Transplant 2010 Dec;16(12):1665-73
Date
07/28/2010Pubmed ID
20659573Pubmed Central ID
PMC3437935DOI
10.1016/j.bbmt.2010.07.014Scopus ID
2-s2.0-78149410631 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Graft-versus-host disease (GVHD) is a major risk factor for secondary malignancy after hematopoietic stem cell transplantation. Squamous cell carcinoma (SCC) of the skin and mucous membranes are especially frequent in this setting where aneuploidy and tetraploidy are associated with aggressive disease. The current study is directed at the mechanism of neoplasia in this setting. Unmanipulated keratinocytes from areas of oral GVHD in 9 patients showed tetraploidy in 10% to 46% of cells when examined by florescein in situ hybridization (FISH). Keratinocytes isolated from biopsy sites of GVHD but not from normal tissue showed even greater numbers of tetraploid cells (mean = 78%, range: 15%-85%; N = 9) after culture. To mimic the inflammatory process in GVHD, allogeneic HLA-mismatched lymphocytes were mixed with normal keratinocytes. After 2 weeks, substantial numbers of aneuploid and tetraploid cells were evident in cultures with lymphocytes and with purified CD8 but not CD4 cells. Telomere length was substantially decreased in the lymphocyte-treated sample. No mutations were present in the p53 gene, although haploinsufficiency for p53 due to the loss of chromosome 17 was common in cells exposed to lymphocytes. These findings suggest that in GVHD, inflammation and repeated cell division correlate with the development of karyotypic abnormalities.
Author List
Sloand EM, Pfannes L, Ling C, Feng X, Jasek M, Calado R, Tucker ZC, Hematti P, Maciejewski J, Dunbar C, Barrett J, Young NAuthor
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultCD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Carcinoma, Squamous Cell
Chromosome Aberrations
Chromosome Deletion
Chromosomes, Human, Pair 17
Coculture Techniques
Female
Genes, p53
Graft vs Host Disease
HLA Antigens
Hematopoietic Stem Cell Transplantation
Humans
Keratinocytes
Leukemia
Lymphocytes
Male
Middle Aged
Ploidies
Skin Neoplasms
Smith-Magenis Syndrome
Telomere
Young Adult
