Expression of B cell-associated transcription factors in B-cell precursor acute lymphoblastic leukemia cells: association with PU.1 expression, phenotype, and immunogenotype.
Expression of B cell-associated transcription factors in B-cell precursor acute lymphoblastic leukemia cells: association with PU.1 expression, phenotype, and immunogenotype.
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B 细胞前体急性淋巴细胞白血病细胞中 B 细胞相关转录因子的表达：与 PU.1 表达、表型和免疫基因型的关联。
DOI：
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发表时间：
2000
影响因子：
2.1
通讯作者：
H. Shiku
中科院分区：
文献类型：
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作者：
K. Nishii;K. Kita;H. Miwa;M. Shikami;M. Taniguchi;E. Usui;N. Katayama;H. Shiku
B 淋巴细胞发育经历多个离散阶段，其特征是免疫球蛋白 (Ig) 位点的规则 DNA 重排，导致 Ig 基因转录和 B 细胞抗原受体表达。这些发育过程也可以通过特定细胞表面标记的表达来区分。因此，Ig、T 细胞受体 (TCR) 基因和表面标记的重排通常被认为是淋巴增殖性疾病中 B 细胞和 T 细胞谱系的有用标记。然而，在最不成熟的淋巴恶性肿瘤（谱系杂乱）中，已报道了 Ig 和 TCR 基因的伴随重排（双基因型），主要是 B 细胞前体急性淋巴细胞白血病（pre-B ALL），但其机制尚不完全清楚。 DNA 重排和特定细胞表面标记受多种特定转录因子的调节。为了更好地表征谱系混杂性，我们研究了淋巴相关转录因子的表达、表型和免疫基因型之间的关系。在 37% 的前 B ALL 样本和所有 B 细胞慢性淋巴细胞白血病 (B-CLL) 样本中发现了 Ig 轻链 kappa 基因重排。 40% 的 B ALL 前样本中显示出 TCR gamma 基因重排，但在任何 B-CLL 样本中均未检测到。在测试的 B 细胞相关转录因子中，Pax5 和 E47 基因在所有 pre-B ALL 和 B-CLL 样本中表达。 RAG-1 基因在所有 B 前 ALL 样品中表达，但在 B-CLL 样品中不表达。 Oct-2 基因在 82% 的 pre-B ALL 和所有 B-CLL 样本中表达。 PU.1 基因在 56% 的 pre-B ALL 样本中表达，但在 B-CLL 样本中不表达。有趣的是，不表达PU.1基因的pre-B ALL样本显示出明显高频率的TCR gamma基因重排。 Oct-2基因表达没有发现这种现象。这些发现表明，PU.1 表达缺失可能会导致谱系杂乱，例如 pre-B ALL 细胞中 Ig 和 TCR 基因同时重排。
B-lymphocyte development progresses through discrete stages characterized by regular DNA rearrangements of the immunoglobulin (Ig) loci that lead to the transcription of Ig genes and expression of B-cell antigen receptors. These developmental processes can also be distinguished by the expression of specific cell-surface markers. Therefore, rearrangement of the Ig, T-cell receptor (TCR) genes, and surface markers are generally considered as useful markers of the B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangement of Ig and TCR genes (double genotype) has been reported in the most immature lymphoid malignancies (lineage promiscuity), mainly in B-cell precursor acute lymphoblastic leukemia (pre-B ALL), but the mechanism is not fully understood. DNA rearrangements and specific cell-surface markers are regulated by several specific transcription factors. To better characterize the lineage promiscuity, we studied the relationship among the expression of lymphoid-associated transcription factors, phenotype, and immunogenotype. Rearrangement of the Ig light chain kappa gene was found in 37% of pre-B ALL samples and in all B-cell chronic lymphocytic leukemia (B-CLL) samples. Rearrangement of TCR gamma gene was shown in 40% of pre-B ALL samples but was not detected in any of the B-CLL samples. Among the tested B cell-associated transcription factors, Pax5 and E47 genes were expressed in all pre-B ALL and B-CLL samples. RAG-1 gene was expressed in all pre-B ALL samples but not in the B-CLL samples. Oct-2 gene was expressed in 82% of pre-B ALL and all B-CLL samples. The expression of PU.1 gene was shown in 56% of pre-B ALL but not in the B-CLL samples. Interestingly, the samples of pre-B ALL, which did not express the PU.1 gene, showed a significantly high frequency of TCR gamma gene rearrangement. This phenomenon was not found with Oct-2 gene expression. These findings suggest that absence of PU.1 expression may result in lineage promiscuity, such as the simultaneous rearrangements of Ig and TCR genes in pre-B ALL cells.