Submitted February 22, 2008
Accepted June 17, 2008
Expansion of a donor-derived hematopoietic stem cell with PIG-A mutation associated with late graft failure after allogeneic stem cell transplantation
Kanako Mochizuki, Chiharu Sugimori, Zhirong Qi, Xuzhang Lu, Akiyoshi Takami, Ken Ishiyama, Yukio Kondo, Hirohito Yamazaki, Hirokazu Okumura, and Shinji Nakao*
Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
* Corresponding author; email: snakao{at}med3.m.kanazawa-u.ac.jp.
A small population of CD55-CD59- blood cells was detected in a patient who developed donor-type late graft failure after allogeneic stem cell transplantation (SCT) for treatment of aplastic anemia (AA). Chimerism and PIG-A gene analyses showed the paroxysmal nocturnal hemoglobinuria (PNH)-type granulocytes to be of a donor-derived stem cell with a thymine insertion in PIG-A exon 2. A sensitive mutation-specific PCR-based analysis detected the mutation exclusively in DNA derived from the donor bone marrow (BM) cells. The patient responded to immunosuppressive therapy and achieved transfusion independence. The small population of PNH-type cells was undetectable in any of the 50 SCT recipients showing stable engraftment. The de novo development of donor-cell derived AA with a small population of PNH-type cells in this patient supports the concept that glycosyl phosphatidylinositol anchored protein deficient stem cells have a survival advantage in the setting of immune mediated BM injury.
