Institute of Hematology, Medical College, Jinan University, Guangzhou, People's Republic of China.
J Hematol Oncol. 2011 May 6;4:21. doi: 10.1186/1756-8722-4-21.
Recently, we clarified at the molecular level novel chromosomal translocation t(14;14)(q11;q32) in a case of Sézary syndrome, which caused a rearrangement from TRAJ7 to the PPP2R5C gene. PPP2R5C is one of the regulatory B subunits of protein phosphatase 2A (PP2A). It plays a crucial role in cell proliferation, differentiation, and transformation. To characterize the expression and distribution of five different transcript variants of the PPP2R5C gene in leukemia, we analyzed the expression level of PPP2R5C in peripheral blood mononuclear cells from 77 patients with de novo leukemia, 26 patients with leukemia in complete remission (CR), and 20 healthy individuals by real-time PCR and identified the different variants of PPP2R5C by RT-PCR.
Significantly higher expression of PPP2R5C was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls. High expression of PPP2R5C was detected in the B-ALL group; however, no significant difference was found compared with the healthy group. The expression level of PPP2R5C in the CML-CR group decreased significantly compared with that in the de novo CML group and was not significantly different from the level in the healthy group. By using different primer pairs that covered different exons, five transcript variants of PPP2R5C could be identified. All variants could be detected in healthy samples as well as in all the leukemia samples, and similar frequencies and distributions of PPP2R5C were indicated.
Overexpression of PPP2R5C in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia.
最近,我们在 Sézary 综合征病例中从分子水平阐明了一种新的染色体易位 t(14;14)(q11;q32),该易位导致 TRAJ7 重排到 PPP2R5C 基因。PPP2R5C 是蛋白磷酸酶 2A(PP2A)的调节 B 亚基之一。它在细胞增殖、分化和转化中起着至关重要的作用。为了描述 PPP2R5C 基因的五个不同转录变体在白血病中的表达和分布,我们通过实时 PCR 分析了 77 例初发白血病患者、26 例完全缓解(CR)白血病患者和 20 例健康个体外周血单个核细胞中 PPP2R5C 的表达水平,并通过 RT-PCR 鉴定了 PPP2R5C 的不同变体。
与健康对照组相比,AML、CML、T-ALL 和 B-CLL 组中 PPP2R5C 的表达明显升高。B-ALL 组中检测到 PPP2R5C 的高表达;然而,与健康组相比,差异无统计学意义。与初发 CML 组相比,CML-CR 组 PPP2R5C 的表达水平显著降低,与健康组无显著差异。使用覆盖不同外显子的不同引物对,可以鉴定出 PPP2R5C 的五个转录变体。所有变体均能在健康样本和所有白血病样本中检测到,并且表明 PPP2R5C 的频率和分布相似。
PPP2R5C 在 T 细胞恶性肿瘤以及髓系白血病细胞中的过度表达可能与其增殖和分化有关。该基因的靶向抑制作用的研究可能有助于进一步阐明白血病的分子机制和靶向治疗。