1. Introduction

The analysis of T cell receptor (TCR), especially the variable region of TCR beta chain (Vβ), is one of the sensitive methods to identify the clonal expansion T cells which response to tumor associated antigens. Clonally expanded T cells can recognize tumor cells in patients with leukemia. Leukemia-associated clonal expansion of TCR Vβ gene families were detected in the past fifteen years, including the predominant usages of TCR Vβ gene families. In this paper, we extracted and reanalyzed the data related to the predominant usages of TCR Vβ, and hoped the finding could present new ideas for the researchers in future studies.

2. Review of the Literature

In the present study, ten reports [1-10]^[1] were selected as the references for reanalysis, and the including criteria was that the predominant usage TCR Vβ genes were clearly stated in the reports; or it would be excluded. The diseases contained acute promyelocytic leukemia (APL), T cell-acute lymphoblastic leukemia (T-ALL), B cell-acute lymphoblastic leukemia (B-ALL), acute monoblastic leukemia (AML), acute myelogenous leukemia (AMOL) and chronic myeloid leukemia (CML).

In the analysis progress, we found that there were Vβ subfamilies in some reports, for example, Vβ5 contained Vβ5.1 and Vβ5.2, Vβ13 contained Vβ13.1 and Vβ13.2. This probably caused by the different classification standards, but the main Vβ gene families were consistent with each other. Therefore, we took the numbers of Vβ subfamilies together as total of the main Vβ gene family. Besides, a concept of predominant usage frequency (frequencies) (PUF or PUFs) was applied, and the formula was as following:

Σn: the summary of the times for certain a Vβ gene; Σp: the summary of the patients with certain a disease or all the patients in the study.

As shown in Table 1, the TCR Vβ genes with the highest PUFs in APL were Vβ12, Vβ21 and Vβ23, which PUFs were all 19.1%; Vβ1, Vβ3, Vβ10, Vβ15 and Vβ18 were next to them with the same PUFs of 14.3%. The predominant expression gene in T-ALL was Vβ15 with PUF of 42.9%; Vβ1, Vβ5 and Vβ10 were the second usage genes which PUFs were all 28.6%. In B-ALL, the gene of the highest PUF (28.6%) was Vβ2; Vβ3 was next to it (19.2%). In AML, Vβ3 was the highest clonal gene (16.7%), which followed by Vβ9 and Vβ23 (Both PUFs were 13.9%). PUF of Vβ2 was high to 66.7% in AMOL, and that of Vβ7 was only 22.2%. The highest usage gene in CML was Vβ3 which PUF was 18.5%; those of Vβ13 and Vβ21 were both 14.8%.

According to PUFs of 24 TCR Vβ gene families specific to the different diseases, the histograms were designed (Figure 1). The x axis represented the PUF of every the TCR Vβ gene, and the y axis represented the 24 TCR Vβ gene families.

Table 1. The summary for the PUFs of 24 Vβ gene families in PBMC of the patients with leukemia (%)

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Figure 1. Different “keys” specific to different diseases formed with the predominant usage frequencies of TCR Vβ genes in PBMC of the corresponding patients

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3. Discussion

In all the six leukemia, the TCR Vβ gene families with the highest PUFs were different to a certain extent. For example, The TCR Vβ genes with highest PUFs were Vβ12, Vβ21 and Vβ APL, while that was Vβ T-ALL, Vβ B-ALL. These different or similar highest predominantly used genes combing the other predominant expression genes formed a combination of Vβ genes. In APL, the combination was Vβ1-Vβ2-Vβ3-Vβ4-Vβ5-Vβ6-Vβ8-Vβ10-Vβ12-Vβ13-Vβ15-Vβ17- Vβ18-Vβ20-Vβ21-Vβ22-Vβ23; in B-ALL, it was Vβ3-Vβ5-Vβ9-Vβ10-Vβ13- Vβ14- Vβ15-Vβ19-Vβ21-Vβ23-Vβ24; in AMOL, those were Vβ2-Vβ7-Vβ9-Vβ21. There were different complications in different types of leukemia, and in our opinions, the complications probably represent the different features specific to the corresponding diseases.

In order to directly observe the characters consisted of the advantageously clonal genes, the histograms were made up according to PUFs of TCR Vβ specific to the different diseases. The columns with different heights represented the PUFs of Vβ subfamilies, which contained monoclonal, biclonal and oligoclonal expression. Obviously, the histogram for each of the leukemia looked like a key, and every column liked its kit. Thus there were different kits for different leukemia, and the kits for a key liked the combination of different TCR Vβ genes mentioned in the above paragraph. Except the combination, the height of the column determined by PUF also could reflect the characters of the TCR Vβ specific to certain a disease. The higher the frequency of the TCR Vβ gene family was, the higher the kit of the key would be. Therefore, to some extent, the key represented the total characterization of TCR Vβ for the patients with leukemia. In anther words, the key was specific to the corresponding leukemia. Of course, the studies on the skewness of TCR Vβ of the patients with leukemia were little, and the key found in this paper could not exactly show the complete specificity of TCR Vβ for each of leukemia. However, through such a reanalysis of the data, we think that there should be a key specific to every disease, including various pathogen infections, type I diabetes, colorectal cancer, and so on. Once the keys of TCR Vβ specific to the diseases are found through the studies on lots of cases in future, in our opinions, it will be benefit to the diagnosis and the exposure of the mechanism for the diseases.

4. Conclusion

Through the reanalysis of the data in the articles related to TCR Vβ predominant usage, we found the features of the usage in each of the disease. The histogram, drawn with the predominant usage frequencies of the TCR Vβ, like a key which specific to the corresponding disease. These results probably pose a new idea for analyzing the skewness of TCR for the researchers of the relative study field.

5. Financial Disclosure

The work is supported by the Provincial Science and Technology Development Project (No. 18054), the Provincial Nature Science Foundation (No. ZR2012HL29), the Project of Shandong Province Higher Educational Science and Technology Program (No. J11LF18), the Population and Family Planning Commission (No. [2011]13), and the Development Plan Project of Jining Science and Technology Bureau of Shandong Province (No. [2011]57, 2014jnjc12 and 2014jnyx14).

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