| Summary: | 碩士 === 臺灣大學 === 醫學檢驗暨生物技術學研究所 === 98 === PAX5 (Paired box 5), a member of PAX gene family, is expressed in the central nervous and the hematopoietic systems and is known to play an important role in B cell commitment. Childhood acute lymphoid leukemia (ALL) is a malignant disease resulting from uncontrolled proliferation of lymphoid progenitors. In previous large-scaled study, the PAX5 gene was the most frequent target of somatic mutation, being altered in about 30% in both pediatric and adult patients with B-ALL. However, whether PAX5 mutation plays an important role in B-ALL leukemogenesis remains uncharacterized. In this study, we intend to investigate the molecular or clinical characteristics of PAX5 expression alteration in B-ALL.
The RNA and protein expression, DNA status (loss of heterozygosity, LOH) of PAX5 gene, as well as clinical data were investigated in 25 diagnostic bone marrow samples obtained from childhood B-ALL patients. Peripheral blood mature B cells obtained from 3 healthy subjects were used as control. Decreased PAX5 mRNA expression was noted in 14 out of 25 leukemic samples as compared to normal mature B cells (median (25%-75%), ALL: 0.4 (0-0.9), Normal: 0.9 (0.9-1), p=0.1438). Although it was not statistically significant, it revealed that the leukemic cells with decreased level of PAX5 mRNA expression tend to carry more non-B markers. There were more mRNAs with variant sizes in leukemic cells than in normal mature B cells. PAX5 protein level was also investigated in the leukemic cells of 7 B-ALL patients. Four showed decreased PAX5 expression and the other 3 were of comparable PAX5 level as compared to normal mature B cells. We also investigated LOH of PAX5 locus in 6 paired-samples (leukemic bone marrow cells and remission peripheral blood cells as normal reference) from B-ALL patients via short tandem repeat analysis. Three showed LOH and one remained heterozygous. The DNA status was not correlated with mRNA expression level. In summary, the trend of decreased PAX5 protein expression was parallel to that of PAX5 mRNA expression level, but is not correlated with DNA status. The results indicate that: 1. PAX5 mRNA expression is generally decreased in B-ALL patients; 2. There were more PAX5 C-terminal variant forms present in B-ALL leukemic samples, including transcript without exons 7 and 8, which may influence trans-activating ability of PAX5; 3. Significantly decreased protein level in 14 out of 25 B-ALL patients reveals the association in B-ALL and decreased PAX5 expression; 4. Besides the gene dosage, some other factors could regulate PAX5 transcription through mechanisms awaited further studies.
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