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

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.