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SOX11在慢性淋巴细胞白血病中的表达与不良预后标志物相关。

SOX11 expression in chronic lymphocytic leukemia correlates with adverse prognostic markers.

作者信息

Roisman Alejandro, Stanganelli Carmen, Nagore Virginia Palau, Richardson Guillermo Videla, Scassa María Elida, Bezares Raimundo Fernando, Cabrejo María, Slavutsky Irma

机构信息

Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, J.A. Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina.

出版信息

Tumour Biol. 2015 Jun;36(6):4433-40. doi: 10.1007/s13277-015-3083-1. Epub 2015 Jan 22.

Abstract

The transcription factor SOX11 plays an important role in embryonic neurogenesis and tissue remodeling. Recent studies have shown aberrant expression of SOX11 in various types of aggressive B cell neoplasms. In this study, we have analyzed SOX11 transcription levels in 86 patients with diagnosis of chronic lymphocytic leukemia (CLL). Results were correlated with well-known prognostic factors such as immunoglobulin heavy chain variable (IGHV) gene mutational status, cytogenetics risk groups and clinicopathological characteristics of the disease. Overall, 35 % of cases showed SOX11 expression; meanwhile, the remaining 65 % lacked gene expression. The analysis taking into account the IGHV mutational status showed significant differences in SOX11 transcripts levels between mutated (0.004 ± 0.0001) and unmutated CLL patients (0.405 ± 0.011) (p < 0.0001), as well as a positive correlation between SOX11 mRNA expression and the percentage of IGHV homology (p = 0.0001). Furthermore, significantly lower SOX11 mRNA expression was detected in patients with deletion 13q14 as a single alteration (0.016 ± 0.008) than those observed in cases with deletions 11q/17p (0.35 ± 0.017) (p = 0.02). The correlation of gene expression with clinical evolution showed shorter treatment free survival (p = 0.043) and overall survival (p = 0.047) in SOX11 positive patients compared to SOX11 negative cases. Our findings show for the first time an association between SOX11 expression and some CLL poor prognostic factors. These results suggest SOX11 as a possible biomarker that adds new biological information that could contribute to a better understanding of this pathology.

摘要

转录因子SOX11在胚胎神经发生和组织重塑中发挥重要作用。最近的研究表明,SOX11在各种侵袭性B细胞肿瘤中表达异常。在本研究中,我们分析了86例慢性淋巴细胞白血病(CLL)患者的SOX11转录水平。结果与免疫球蛋白重链可变区(IGHV)基因突变状态、细胞遗传学风险组和疾病的临床病理特征等众所周知的预后因素相关。总体而言,35%的病例显示SOX11表达;同时,其余65%缺乏基因表达。考虑到IGHV突变状态的分析显示,突变的CLL患者(0.004±0.0001)和未突变的CLL患者(0.405±0.011)之间的SOX11转录水平存在显著差异(p<0.0001),并且SOX11 mRNA表达与IGHV同源性百分比之间存在正相关(p=0.0001)。此外,作为单一改变的13q14缺失患者(0.016±0.008)的SOX11 mRNA表达明显低于11q/17p缺失患者(0.35±0.017)(p=0.02)。基因表达与临床进展的相关性显示,与SOX11阴性患者相比,SOX11阳性患者的无治疗生存期(p=0.043)和总生存期(p=0.047)更短。我们的研究首次表明SOX11表达与一些CLL不良预后因素之间存在关联。这些结果表明SOX11可能是一种生物标志物,它增加了新的生物学信息,有助于更好地理解这种病理学。

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