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St. Jude researchers have shown that it might be possible to significantly improve a commonly accepted technique used to identify the best donors of stem cells, which are used to help treat leukemia. Following eradication of a patient’s leukemic cells, donor stem cells rebuild the populations of red and white cells.
The technique is used to determine if natural killer immune cells (NK cells) arising from donated stem cells will be effective in attacking leukemic cells in the recipient. Donor NK cells offer an extra boost to the treatment of leukemia by recognizing and killing leukemic cells remaining after chemotherapy and irradiation—the so-called graft-versus-leukemia effect. A report on this study appears in the May 15 issue of The Journal of Immunology and currently appears online.
To determine whether a particular donor’s NK cells will work in a specific recipient, clinicians look for specific proteins, called killer immunoglobin-like receptors (KIR) on the surface of a donor’s own NK cells. By comparing KIR proteins on donor NK cells with certain proteins called ligands on the cells of the recipient, clinicians can predict whether the NK cells will attack leukemic cells in the recipient.
A common technique for determining which KIR proteins a donor’s NK cells will have is to search for genes that code for those proteins, according to Rupert Handgretinger, MD, PhD, director of Stem Cell Transplantation. But the presence of a gene or genes for particular KIR proteins should not be used as the only proof that these NK cells will have the corresponding proteins on their surface, Handgretinger noted.
“The reality of genes and KIR proteins is much more complicated,” said Wing Leung, MD, PhD, of Hematology-Oncology and the lead author of the study. “We found that a significant number of donors—25 percent—can have a gene for one of the important KIR proteins, even though their NK cells don’t carry those proteins on their surfaces. So you can’t assume that an NK cell will have a particular KIR protein just because the gene is present.”
The St. Jude team also found that when two specific KIR genes called KIR2DL2 and KIR2DL3 are both present, KIR2DL3 is often the only one that is expressed. This further complicates prediction of which KIR proteins will be on NK donor cells, Handgretinger said.
Finally, the investigators also found that even if a gene were present, and was actually expressed, the amount of protein produced might be insignificant.
The team concluded that using a common laboratory technique called flow cytometry analysis to directly identify the KIR proteins on NK cells is a more accurate way to predict whether a donor’s NK cells should be transplanted into a specific patient. “Choosing the right donor may reduce the risk of leukemia relapse by more than 70 percent,” Leung said.
Other authors include Rekha Iyengar; Brandon Triplett, MD; and James Houston, all of Hematology-Oncology; Victoria Turner, PhD, and Frederick Behm, PhD, both of Pathology; and Marti Holladay, Stem Cell Transplantation.
Last update: July 2005