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Journal List > Korean J Hematol > v.41(3) > 1032666

Kim, Choi, Jeong, Min, Kim, and Kim: Killer Cell Immunoglobulin-like Receptor (KIR) Analysis in Adult Korean Patients with Acute Myeloid Leukemia

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.

Conclusion:

These results indicate that the expressions of donor inhibitory and activating repertoire of KIR genotypes, even in the HLA-matched sibling setting, are unique parameters to be considered when we perform allogeneic sibling HSCT.

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REFERENCES

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kjh-41-139f1.tif
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.
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Table 1.
Summarized data of KIR genotyping from normal transplantation donors in this study (n=76)
Genotype 2DL 2DS 3DL 3D-S1 2D-P1 3DP No. of KIR genes Genotypes
1 2 3 4 5AB 5A 5B 1 2 3 4 4v 5 1 2 3 1 1v No. %
1                   8 14 18.4
2                     8 14 18.4
3             11 5 6.6
4             11 5 6.6
5                     8 5 6.6
6                       7 4 5.3
7                       7 3 3.9
8             11 3 3.9
9             11 3 3.9
10                     7 2 2.7
11           12 2 2.7
12                 8 2 2.7
13           11 2 2.7
14           12 1 1.3
15                 9 1 1.3
16             11 1 1.3
17                   8 1 1.3
18                 9 1 1.3
19                 9 1 1.3
20           12 1 1.3
21             10 1 1.3
22                             4 1 1.3
23                     8 1 1.3
24           11 1 1.3
25           11 1 1.3
Table 2.
Summarized data of KIR genotyping from acute myelogenous leukemia patients in this study (n=92)
Genotype 2DL 2DS 3DL 3D-S1 2D-P1 3DP No. of KIR genes Genotypes
1 2 3 4 5AB 5A 5B 1 2 3 4 4v 5 1 2 3 1 1v No. %
1                   8 15 16.3
2                     8 13 14.1
3                       7 7 7.6
4                     7 6 6.5
5             11 5 5.3
6             11 5 5.3
7                     8 4 4.3
8                       7 3 3.2
9             11 2 2.2
10           12 2 2.2
11                 9 2 2.2
12           11 2 2.2
13           11 2 2.2
14                 9 2 2.2
15               9 2 2.2
16             11 2 2.2
17               10 2 2.2
18             11 1 1.1
19         12 1 1.1
20                   8 1 1.1
21                 9 1 1.1
22           11 1 1.1
23       13 1 1.1
24           11 1 1.1
25                       7 1 1.1
26                       7 1 1.1
27           11 1 1.1
28       12 1 1.1
29           11 1 1.1
30             11 1 1.1
31             11 1 1.1
32               10 1 1.1
33             11 1 1.1
Table 3.
Summarized data of KIR genotyping from all enrolled individuals in this study (n=168)
Genotype 2DL 2DS 3DL 3D-S1 2D-P1 3DP No. of KIR genes Genotypes
1 2 3 4 5AB 5A 5B 1 2 3 4 4v 5 1 2 3 1 1v No. %
1                   8 29 17.3
2                     8 27 16.1
3                       7 11 6.5
4             11 10 5.9
5             11 10 5.9
6                     8 9 5.4
7                     7 8 4.8
8                       7 6 3.6
9             11 5 3.0
10             11 4 2.4
11           12 3 1.7
12                 9 3 1.7
13           11 3 1.7
14           12 2 1.2
15         12 2 1.2
16           11 2 1.2
17               10 2 1.2
18                 9 2 1.2
19               9 2 1.2
20             11 2 1.2
21                   8 2 1.2
22                 9 2 1.2
23                 10 2 1.2
24                 9 1 0.6
25           12 1 0.6
26             10 1 0.6
27             11 1 0.6
28           11 1 0.6
29               10 1 0.6
30       13 1 0.6
31             11 1 0.6
32                             4 1 0.6
33           11 1 0.6
34                       7 1 0.6
35                     8 1 0.6
36           11 1 0.6
37                       7 1 0.6
38           11 1 0.6
39       12 1 0.6
40             11 1 0.6
41           11 1 0.6
42             11 1 0.6
43           11 1 0.6
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