Association of KIR2DS4 and its variant KIR1D with leukemia

Giebel, Sebastian; Nowak, Izabela; Wojnar, Jerzy; Krawczyk-Kuliś, Małgorzata; Hołowiecki, Jerzy; Kyrcz‐Krzemień, Sławomira; Kuśnierczyk, Piotr

doi:10.1038/leu.2008.108

Cited by 33 publications

(21 citation statements)

References 8 publications

(21 reference statements)

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“…It is noteworthy that all the previous studies 13,17,34,35 examined associations between KIR genes and adult-onset leukemia. Because the present study was focused on childhood-onset leukemia, direct comparisons between it and the earlier studies may not be valid and conclusive.…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were considered positive for the gene when a nonmutated amplicon band was seen on the gel with or without the presence of the mutated band. In another study conducted in Polish and German individuals, Giebel et al 17 found a protective association between the KIR2DS4 gene and chronic myeloid leukemia, but no associations with ALL were evident. Similar to the previous study, the lack of association with ALL may have been the result of the small number of ALL patients (n ϭ 21) investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these haplotypes lack KIR2DS4 but contain 1 or more of the other 5 activating KIR genes. Several studies have shown that KIR genotypes and the number of activating KIR genes inherited by a person may affect resistance/susceptibility to infectious agents, development of autoimmune diseases, reproductive efficiency, GVHD, and cancer [17][18][19][20][21][22] (reviewed in Kulkarni et al 23 and Farag et al 24 ). As mentioned above, they have also been shown to protect humans from certain types of leukemia.…”

Section: Introductionmentioning

confidence: 99%

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Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia

Almalte

Samarani

Iannello

et al. 2011

Blood

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Acute lymphoblastic leukemia of pre-B cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/ resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest. Humans may inherit different numbers of the 6 distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to the development of B-ALL. We addressed this issue by performing a case-control study in Canadian children of white origin. Our results show that harboring activating KIR genes is associated with reduced risk for developing B-ALL in these children. Of the 6 activating KIR genes, KIR2DS2 was maximally associated with decreased risk for the disease (P ‫؍‬ 1.14 ؋ 10 ؊7 ). Furthermore, our results showed that inheritance of a higher number of activating KIR genes was associated with significant reductions in risk for ALL in children. These results were also consistent across different ALL phenotypes, which included children with pre-T cell ALL. Our study provides novel insights concerning the pathogenesis of childhood leukemia in white children and has implications for the development of new immunotherapies for this cancer. (Blood. 2011;118(5): 1323-1328)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia

Almalte

Samarani

Iannello

et al. 2011

Blood

View full text Add to dashboard Cite

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“…The combination of KIR2DS4 and KIR2DS4del was associated with disease progression from hepatitis to hepatocellular carcinoma (HCC) development via cirrhosis (26). In terms of malignant diseases, Giebel et al (27) reported that the absence of KIR2DS4full was associated with susceptibility to chronic myeloid leukemia, but the effect of KIR2DS4full appeared to be the opposite in endometrioid ovarian cancer (28). Although the associations of all known 15 human KIRs and their known HLA ligands with the prognosis of mNSCLC were evaluated in the present study, we only observed that the KIR2DS4full-positive/KIR2DS4del-negative type combined with its potential ligand HLA-C1 was significantly associated with improved OS in the univariate analysis (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer

Liu

Sansas

et al. 2016

Molecular and Clinical Oncology

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Abstract. Non-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth. Natural killer (NK) cells play a pivotal role in immunological surveillance. Activation of NK cells partially depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. We herein investigated the association of KIRs and HLA ligands with survival in metastatic NSCLC (mNSCLC) patients treated with chemotherapy in a Chinese Han population. Polymerase chain reaction with sequence-specific primers was used to type 15 KIRs at the DNA and mRNA level and 6 HLA ligands in 70 mNSCLC patients. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression model was applied for multivariate survival analysis, with the stepwise selection, to determine independent predictors of survival. It was observed that patients with KIR2DS4del gene expression at the mRNA level or HLA-Bw4T80 exhibited poor overall survival (OS). The multivariate analysis revealed that HLA-Bw4T80 and KIR2DS4del expression were independent predictors of OS. This observation indicated that the KIR/HLA ligand is a promising predictor of survival in mNSCLC and may also provide a strategy for treatment stratification and patient management. IntroductionNon-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth (1). Natural killer (NK) cells play a pivotal role in innate immunity and immunological surveillance (2). Activation of NK cells partly depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands (3). KIRs are a family of cell surface receptors expressed by NK cells and certain subpopulations of T lymphocytes. The KIR family consists of inhibitory as well as activating receptors characterized by both allelic (high numbers of variants) and haplotypic (different numbers of genes for inhibitory and activating receptors on individual chromosomes) polymorphisms (4). The ligands of KIRs are specific epitopes on HLA class I molecules (5). HLA-C allotypes fall into the C1 or C2 groups (asparagine and lysine, respectively, at position 80) that are recognized by KIR2DL2/KIR2DL3 and KIR2DL1/KIR2DS1, respectively. Two previous studies have implicated HLA-C1 and HLA-C2 as potential ligands for KIR2DS4 (6,7). KIR3DL1/KIR3DS1 recognizes HLA-Bw4 epitopes of HLA-A and HLA-B alleles, which are classified according to whether isoleucine or threonine is present at position 80 (4).An increased understanding of the complexities of the biology of the KIR/HLA system has provided opportunities to leverage NK cell function as a novel avenue of immunotherapy for cancer (8 HLA, human leukocyte antigen; NK, natural killer; NSCLC, non-small-cell lung cancer; mNSCLC, metastatic non-small-cell lung cancer; SSP-PCR, sequence-specific primer polymerase chain reaction;...

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“…2 Following their suggestion, we additionally analyzed chronic myelogenous leukemia (CML) patients and their donors with regard to homozygosity for haplotype A and killer immunoglobuline-like receptor (KIR)1D to identify subjects lacking any functional activating KIR. In the respective groups, the frequencies were 25.8 and 16.1%.…”

Association of KIR2DS4 and its variant KIR1D with leukemia

Cited by 33 publications

References 8 publications

Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia

Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia

Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer

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