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BCL11A在慢性淋巴细胞白血病中的表达

Expression of BCL11A in chronic lymphocytic leukaemia.

作者信息

Tosic Natasa, Ugrin Milena, Marjanovic Irena, Kostic Tatjana, Vukovic Vojin, Tomic Kristina, Otasevic Vladimir, Antic Darko, Mihaljevic Biljana, Pavlovic Sonja, Karan-Djurasevic Teodora

机构信息

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.

Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia.

出版信息

Int J Lab Hematol. 2023 Feb;45(1):64-71. doi: 10.1111/ijlh.13969. Epub 2022 Sep 19.

Abstract

INTRODUCTION

The B-cell lymphoma/leukaemia 11A (BCL11A) gene encodes a Krüppel-like transcription factor involved in lymphocyte development during normal haematopoiesis. Aberrant expression of BCL11A has been observed in several haematological malignancies, including chronic lymphocytic leukaemia (CLL). However, its functions in the regulatory networks of malignant B lymphocytes are poorly understood, as are the relations to clinical course and outcome of B-cell malignancies, particularly CLL.

METHODS

The expression of BCL11A was analysed in peripheral blood mononuclear cells of 87 newly-diagnosed CLL patients by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), and association with clinical and molecular variables was assessed.

RESULTS

BCL11A was significantly overexpressed in CLL samples compared to control samples (p < 0.001). BCL11A expression level exhibited no association with age, sex, leukocyte, lymphocyte and platelet counts, haemoglobin level, serum β2-microglobulin, CD38 status and cytogenetic abnormalities. On the other hand, high BCL11A expression was associated with low serum lactate dehydrogenase (p = 0.031), Binet A stage (p = 0.047) and mutated IGHV (p = 0.028). In addition, a positive correlation with BCL2/BAX mRNA ratio was observed (r = 0.36; p < 0.001). Regarding the association with the time to first treatment (TTFT), a trend towards longer median TTFT in BCL11A high- versus BCL11A low-expressing cases was detected (21 vs. 6 months; p = 0.164).

CONCLUSION

The results of this study show that BCL11A is upregulated in CLL patients, and that high BCL11A expression at diagnosis may be associated with better prognosis. These data are consistent with the role of BCL11A expression in CLL biology, and imply its potential prognostic relevance.

摘要

引言

B细胞淋巴瘤/白血病11A(BCL11A)基因编码一种Krüppel样转录因子,参与正常造血过程中的淋巴细胞发育。在包括慢性淋巴细胞白血病(CLL)在内的几种血液系统恶性肿瘤中已观察到BCL11A的异常表达。然而,其在恶性B淋巴细胞调控网络中的功能以及与B细胞恶性肿瘤,特别是CLL的临床病程和预后的关系仍知之甚少。

方法

通过定量逆转录聚合酶链反应(qRT-PCR)分析87例新诊断CLL患者外周血单个核细胞中BCL11A的表达,并评估其与临床和分子变量的相关性。

结果

与对照样本相比,CLL样本中BCL11A显著过表达(p < 0.001)。BCL11A表达水平与年龄、性别、白细胞、淋巴细胞和血小板计数、血红蛋白水平、血清β2-微球蛋白、CD38状态和细胞遗传学异常均无关联。另一方面,BCL11A高表达与低血清乳酸脱氢酶(p = 0.031)、Binet A期(p = 0.047)和IGHV突变(p = 0.028)相关。此外,观察到与BCL2/BAX mRNA比值呈正相关(r = 0.36;p < 0.001)。关于与首次治疗时间(TTFT)的关联,在BCL11A高表达与低表达病例中检测到中位TTFT有延长趋势(21个月对6个月;p = 0.164)。

结论

本研究结果表明BCL11A在CLL患者中上调,诊断时BCL11A高表达可能与较好的预后相关。这些数据与BCL11A表达在CLL生物学中的作用一致,并暗示其潜在的预后相关性。

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