Donor-derived oral squamous cell carcinoma after allogeneic bone marrow transplantation

• Published in: Blood 2009-02, Vol.113 (8), p.1834-1840
• Main Authors: Janin, Anne, Murata, Hideyuki, Leboeuf, Christophe, Cayuela, Jean-Michel, Gluckman, Eliane, Legrès, Luc, Desveaux, Allison, Varna, Mariana, Ratajczak, Philippe, Soulier, Jean, de Thé, Hugues, Bertheau, Philippe, Socié, Gérard
• Format: Article
• Language: English
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone Marrow Transplantation; Bone Marrow Transplantation - adverse effects; Bone marrow, stem cells transplantation. Graft versus host reaction; Cancer; Carcinoma, Squamous Cell; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Child, Preschool; Female; Graft vs Host Disease; Graft vs Host Disease - complications; Graft vs Host Disease - genetics; Graft vs Host Disease - pathology; Humans; In Situ Hybridization, Fluorescence; Life Sciences; Male; Medical sciences; Mouth Neoplasms; Mouth Neoplasms - etiology; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Otorhinolaryngology. Stomatology; Sex Factors; Tissue Donors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Chimera; Transplantation, Homologous; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-07-171702

In animal models, tissue stem cells were proposed to exhibit an unexpected level of plasticity, although issues on cell fusions have lead to some controversies. Only transplantation experiments using genetically distinct recipients and donors can unequivocally show these changes in cell fate. We have analyzed oral squamous cell carcinomas arising in 8 long-term survivors of allogeneic bone marrow transplantation, in whom chronic graft-versus-host disease greatly favors development of squamous cell carcinomas, possibly as a consequence of lichenoid mucosal inflammation. With the use of 2 independent methods, (1) combined immunostaining and fluorescent in situ hybridization (FISH) analysis for X and Y chromosomes sequences in sex-mismatched grafts and (2) comparison of microsatellite typing of laser-microdissected tumor, donor, and recipient cells, in all tumors, we showed that 4 of these 8 epithelial tumors actually arose from the engrafted allogeneic bone marrow. Thus, donor-derived bone marrow cells, whether hematopoietic or mesenchymal, recruited to sites of chronic mucosal inflammation yielded epithelial tumors. Our observations therefore show that marrow cells in humans have a major role in epithelial cancer formation after allogeneic transplantation.