Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability
Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability
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DOI：
10.1038/sj.leu.2403779
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发表时间：
2005-07-01
期刊：
影响因子：
11.4
通讯作者：
Seifarth, W
中科院分区：
文献类型：
--
作者：
Giehl, M;Fabarius, A;Seifarth, W
中心体异常是各种癌症的标志，与染色体错分离、染色体不稳定和非整倍体有关。由于遗传不稳定性是慢性髓性白血病（CML）的一个共同特征，我们试图研究中心体畸变是否发生，以及是否与CML的疾病分期和细胞遗传学结果相关。我们用中心体特异性抗体检测了34例CML样本，包括18例新诊断的慢性期（CP）和16例原细胞危象（BC）样本的CD34+ Ph+细胞。与相应的CD34_对照细胞相比，所有CP和BC样品均显示中心体改变。在29.1 +/- 5.9%的CP细胞和54.3 +/- 4.8%的BC细胞中检测到中心体异常，而在对照组中仅检测到2.4 +/- 1.1% （P < 0.0001）。仅在1/18 CML-CP患者中发现t（9;22）易位的额外核型改变。相比之下，11/16 (73%)CML-BC患者在48.7%的分析细胞中显示额外的核型改变，与异常中心体状态相关（P = 0.0005）。我们的研究结果表明，中心体缺陷是CML中常见的和早期可检测的特征，可能有助于获得染色体畸变和非整倍体。它们可能被认为是疾病进展的驱动力，可以作为未来的预后指标。
Centrosome abnormalities are hallmarks of various cancers and have been implicated in chromosome missegregation, chromosomal instability, and aneuploidy. Since genetic instability is a common feature in chronic myeloid leukemia (CML), we sought to investigate whether centrosome aberrations occur and correlate with disease stage and cytogenetic findings in CML. We examined 34 CML samples including CD34+ Ph+ cells of 18 newly diagnosed patients (chronic phase (CP)) and 16 blast crisis ( BC) specimens by using a centrosome- specific antibody to pericentrin. All CP and BC samples displayed centrosome alterations as compared with corresponding CD34_ control cells. Centrosome abnormalities were detected in 29.1 +/- 5.9% of CP blasts and in 54.3 +/- 4.8% of BC blasts, but in only 2.4 +/- 1.1% of controls (P < 0.0001). Additional karyotypic alterations to the t(9;22) translocation were found in only 1/18 CML-CP patients. In contrast, 11/16 (73%) CML-BC patients displayed additional karyotype alterations in 48.7% of analyzed cells, correlating with an abnormal centrosome status (P = 0.0005). Our results indicate that centrosome defects are a common and early detectable feature in CML that may contribute to acquisition of chromosomal aberrations and aneuploidy. They may be considered as the driving force of disease progression and could serve as future prognostic markers.