ECONDARY cancer is a well-established longterm complication of bone marrow transplantation. 1-3 These post-transplantation cancers are usually associated with exposure to radiation, other genotoxic agents, or Epstein-Barr virus; in rare cases, they result from the transfer of neoplastic cells in transplanted tissue. 4 We describe two sisters, one the donor and the other the recipient of a bone marrow transplant, in whom subcutaneous panniculitic T-cell lymphoma 5,6 developed three years after the procedure. The finding of identical T-cell clones in the tumors of both sisters implicated the transfer of neoplastic T cells during bone marrow transplantation as the cause of the recipient's subcutaneous lymphoma. CASE REPORTSA 19-year-old woman presented in 1993 with stage IVB, anaplastic large-cell lymphoma of T-cell lineage (Ki-1 lymphoma). She had a complete remission after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone, but lymphomatous meningitis later developed. After conditioning therapy, she received a T-cell-depleted bone marrow transplant from her HLA-identical sister, who was 25 years old, and again entered a remission. She died of an independent lymphoma eight years after the initial diagnosis and seven and a half years after the transplant.Three and a half years after the transplantation, the marrow donor presented with eczematous dermatitis on her legs, a nodule on her left arm, and fever. Biopsy of the nodule revealed lobular lymphocytic panniculitis with perivascular lymphocytes. Biopsy of a persistent nodule on her leg revealed an ulcerated epidermis overlying S a dense lobular subcutaneous infiltrate composed of pleomorphic, atypical lymphocytes that surrounded adipocytes (Fig. 1). The atypical cells were positive for CD3, CD8, granzyme B, and TIA-1 (a granular protein of cytotoxic T cells) and negative for CD56 and CD20. The infiltrate contained a monoclonal population of T cells with rearranged T-cell receptor g ( TCR g ) genes and was negative for Epstein-Barr virus on in situ hybridization.Despite treatment, the donor's cutaneous lesions and constitutional symptoms progressed. A serologic test for human T-cell lymphotropic virus type I was negative, and the results of a serologic test for Epstein-Barr virus were consistent with a history of prior exposure. Evidence of the hemophagocytic syndrome and pancytopenia developed. After two cycles of CHOP chemotherapy, gross gastrointestinal hemorrhage occurred, and the patient died two years after presentation.One month before her sister's death the recipient was seen for a one-year history of skin lesions on her legs. Physical examination showed eczematous plaques and nodules on the lower part of both legs. Histologic examination of a nodule revealed many similarities to the subcutaneous panniculitic T-cell lymphoma identified in her sister, including atypical T cells infiltrating the dermis and subcutis, with rimming of adipocytes. The s...
The ROX3 gene was identified during a hunt for mutants with increased expression of the heme-regulated CYC7 gene, which encodes the minor species of cytochrome c in the yeast Saccharomyces cerevisiae. The rox3 mutants caused a 10-fold increase in CYC7 expression both in the presence and absence of heme, had slightly increased anaerobic expression of the heme-activated CYCI gene, and caused decreases in the anaerobic expression of the heme-repressed ANBI gene and the aerobic expression of its heme-induced homolog. The wild-type ROX3 gene was cloned, and the sequence indicated that it encodes a 220-amino-acid protein. This protein is essential; deletion of the coding sequence was lethal. The coding sequence for j-galactosidase was fused to the 3' end of the ROX3 coding sequence, and the fusion product was found to be localized in the nucleus, strongly suggesting that the wild-type protein carries out a nuclear function. Mutations in the rox3 gene showed an interesting pattern of intragenic complementation. A deletion of the 5' coding region complemented a nonsense mutation at codon 128 but could not prevent the lethality of the null mutation. These results suggest that the amino-terminal domain is required for an essential function, while the carboxy-terminal domain can be supplied in trans to achieve the wild-type expression of CYC7. Finally, RNA blots demonstrated that the ROX3 mRNA was expressed at higher levels anaerobically but was not subject to heme repression. The nuclear localization and the lack of viability of null mutants suggest that the ROX3 protein is a general regulatory factor.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.