BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia
BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia
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DOI：
10.1007/s00277-008-0603-8
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发表时间：
2009-04-01
影响因子：
3.5
通讯作者：
Kimura, Akiro
中科院分区：
文献类型：
--
作者：
Bhattacharyya, Joyeeta;Mihara, Keichiro;Kimura, Akiro
BMI-1 在调节造血干细胞和祖细胞的活性中起着至关重要的作用。即使在甲磺酸伊马替尼出现后，慢性粒细胞白血病（CML）患者仍面临发生急变危象（BC）的风险。在本研究中，为了确定BMI-1与BC的相关性，我们通过流式细胞术研究了慢性期（CP）、加速期（AP）和BC的CD34（+）细胞中BMI-1的表达。有趣的是，CP 中的 BMI-1 表达水平显着高于对照，并且在疾病进展过程中进一步增加（对照 - 5.66％；CP - 36.93％；AP 和 BC - 76.41％）。奇怪的是，在从 CP 到 BC 的疾病进展过程中，BMI-1 的 mRNA 水平几乎一致（对照 2.21；CP-9.77；AP 和 BC-9.70（BMI-1/3-磷酸甘油脱氢酶比率））。由于我们进一步发现，在蛋白酶体抑制剂存在下，人胚胎肾293细胞中BCR-ABL的过度表达增强了BMI-1的表达，并且来自BC患者的K562细胞中的BMI-1表达增加，因此推测BMI-1在疾病进展过程中受到BCR-ABL的正向调节，并进一步受到转录后修饰的正向调节。我们建议将 CD34(+) 细胞中的 BMI-1 表达作为监测 CML 患者的分子标志物。
BMI-1 plays a critical role in regulating the activity of hematopoietic stem and progenitor cells. Patients with chronic myeloid leukemia (CML) are at a risk of developing blastic crisis (BC) even after the emergence of imatinib mesylate. In this study, to determine the relevance of BMI-1 to BC, we investigated the expression of BMI-1 in CD34(+) cells at each of the chronic phase (CP), the accelerated phase (AP), and BC by flow cytometry. Interestingly, the level of BMI-1 expression was significantly higher in CP than in controls and was further increased during the course of the disease progression (control-5.66%; CP-36.93%; AP and BC-76.41%). Curiously, mRNA levels for BMI-1 were almost consistent during the disease progression from CP to BC (control-2.21; CP-9.77; AP and BC-9.70 (BMI-1/glyceraldehyde-3-phosphate dehydrogenase ratio)). Since we further found that overexpression of BCR-ABL in human embryonic kidney-293 cells enhanced BMI-1 expression and that BMI-1 expression was increased in K562 cells, derived from patients with BC, in the presence of proteasomal inhibitors, BMI-1 was presumed to be positively regulated by BCR-ABL and further by posttranscriptional modification in the course of the disease progression. We suggest the usefulness of BMI-1 expression in CD34(+) cells as a molecular marker for monitoring patients with CML.