Elsevier

Leukemia Research

Volume 34, Issue 1, January 2010, Pages 55-58
Leukemia Research

Killer cell immunoglobulin-like receptor gene polymorphisms in patients with leukemia: Possible association with susceptibility to the disease

https://doi.org/10.1016/j.leukres.2009.04.022Get rights and content

Abstract

Accumulating evidences suggest that killer cell immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of diverse kinds of diseases. However, the functions and effects of KIR gene polymorphisms in the development of diseases remain largely unknown, especially about the activating KIR genes. To investigate the association of KIR gene polymorphisms with subtypes of leukemia, we carried out the present study on 263 patients with leukemia and 239 healthy controls by means of polymerase chain reaction-sequence-specific primer and analysis, and then all data were analyzed by Logistic regression method. Our results showed that the frame genotypes of KIR2DL4, 3DL2, 3DL3 and 3DP1 were expressed in all patients and all controls. The genotypes of KIR2DL1, 2DL3, 3DL1, and 2DP1 were most prevalent genotypes whose rates were more than 95% in all patients and all controls. The rate of activating KIR2DS4 was much higher in patients with CML than that in healthy controls (P < 0.001) while the activating KIR2DS3 was lower in patients with ALL compared with healthy controls (P < 0.05). There was no significant change of KIR genes found in patients with NALL. In conclusion, this study suggests that the activating KIR2DS4 may serve as CML susceptive gene to trigger leukemia development, while KIR2DS3 is possibly a protect gene of ALL.

Introduction

Leukemia is one of the common diseases, which threatens people's health severely. It seemed that the incidence rate appeared a rising tendency in China recent years [1]. With the development of molecular immunology with related basic medicine, the relationship between the expression of some predisposing genes, immune response genes, dysfunction of NK cell and the leukemia development and therapy is more and more paid close attention to, although the disease development depended on multiple risk factors.

Natural killer (NK) cells are the fast-acting effector lymphocytes of innate immunity that respond to infection, tumor, and allogeneic hematopoietic cell transplantation while remaining tolerant to healthy cells [2], [3]. The effectors’ function of NK cells is regulated by the dynamic balance between signals transduced from the activating and inhibitory cell surface receptors [4]. A family named KIR is rapidly enveloped which encodes key receptors of human NK cells. Sixteen KIR receptors have been characterized in humans: seven inhibitory types (3DL1–3, 2DL1–3, 2DL5), six activating types (3DS1, 2DS1–5), one (2DL4) with both inhibitory and activating potential and two genes (2DP1 and 3DP1) are pseudogenes that do not encode a functional KIR receptor [5], [6], [7]. There are accumulated research focuses on relationship between KIR gene polymorphisms and hemopoietic stem cell transplantation [8], [9], [10] and the association of KIR gene polymorphisms with diseases [11], [12], [13] while just a few researches on the relationship between KIR gene polymorphisms and the development of leukemia [14], [15]. To exploratively investigate the relationship of KIR with leukemia development, we examined genes encoding KIR receptors in patients with leukemia in China and compared our results to the controls.

Section snippets

Patients

The study group consisted of 263 patients with leukemia who were diagnosed by three major hospitals in Xi’an between 2004 and 2008, including 135 patients with chronic myelogenous leukemia (CML), 67 patients with acute non-lymphoblastic leukemia (NALL) and 61 patients with acute lymphoblastic leukemia (ALL). Of these, there are 94 females and 169 males in study group, ranging in age from 3 to 55 (mean age 28.9). For control group, there are 239 random-selected health blood donor samples from

The expression of KIR gene polymorphisms in patient with leukemia

Framework genes KIR2DL4, 3DL2, 3DL3 and 3DP1 were present in all of the samples. KIR pseudogenes KIR2DP1 was present in most samples (98.1% in patients and 98.7% in controls, respectively). A tendency was found that inhibitory KIR genes have higher expression compared with activating KIR genes in all study samples. Among them, it was a high frequency of inhibitory KIR genes 2DL1, 2DL3, 3DL1, 2DP1 in all samples, which are more than 95% while the frequency of 2DL5B is very low, which is lower

Discussion

The KIR system spans a region of about 150 kb on chromosome 19q13.4 [16], [6]. The number and type of KIR genes arranged on the haplotypes vary greatly, which produce substantial differences between individuals in their KIR gene content. Genotyping studies revealed a significant ethnic difference in KIR gene frequencies, and such disparity is more pronounced with activating KIR genes. A growing number of epidemiological studies suggest that the interactions of KIR receptors and HLA class I

Conflict of interest statement

None.

Acknowledgements

This work was supported by Shaan’Xi Health depart Government grant NO 2008K09-02. Yan Zhang and Bo Wang contributed equally to this work.

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