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Abstract
Background:
The prevalent natural killer (NK) cells induce alloreaction against leukemic cells during post-transplant. NK cell alloreactivity depends on the compatibility of killer cell immunoglobulin-like receptors (KIR) epitopes for graft-versus-host disease. Genotypic expressions of inhibitory or activating KIR in patients with acute myelogenous leukemia (AML) and their HLA-matched sibling donors, as a model for Korean KIR haplotype diversity and NK alloreactivity, were investigated.
Methods:
Ninety-two patients in complete remission and their 76 HLA-matched sibling donors were enrolled in this study. All the patients were scheduled to receive allogeneic hematopoietic stem cell transplantations (HSCT). KIR PCR-SSP typing was performed for 19 different kinds of KIR genes and pseudogenes. The PCR data representing the KIR genotypes from both the patients and donors were compared.
Results:
We found 43 Korean KIR haplotypes. Thirty-three variable haplotypes for the AML patients, in addition to 25 haplotypes for the normal HSCT donors, were demonstrated. Of note, the expressions of specific genes such as 2DL2 (P=0.026), 2DS2 (P=0.042), and 2DS4 (P=0.037) revealed remarkable differences between the patients and the normal donors. Korean HLA-identical sibling pairs showed 38% KIR matches in terms of the gene content and allelic polymorphism. Although the KIR gene content was the same between the patients and the donors, 40% of those matched pairs of patients and donors showed allelic polymorphism, specifically in the context of 2DL5 and 2DS4 genes.
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Fig. 1
KIR genotyping by PCR-SSP in a specific AML patient. Details are described in ‘Materials and Methods’. 1, 2DL1; 2, 2DL2; 3, 2DL3; 4, 2DL4; 5, 2DL5A; 6, 2DL5B∗002/004; 7, 2DL5B∗003; 8, 2DS1; 9, 2DS2; 10, 2DS3; 11, 2DS4∗ 00101/00102/002; 12, 2 DS4∗003; 13, 2DS5; 14, 3DL1; 15, 3DL2; 16, 3DL3; 17, 3DS1; 18, 2DP1; 19, 3DP1∗001/001; 20, 3DP1∗00301/00302; 21, negative control; M, marker.
Table 1.
Summarized data of KIR genotyping from normal transplantation donors in this study (n=76)
Table 2.
Summarized data of KIR genotyping from acute myelogenous leukemia patients in this study (n=92)
Table 3.
Summarized data of KIR genotyping from all enrolled individuals in this study (n=168)
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