c-myb在皮肤T细胞淋巴瘤的白血病和非白血病变体中的过表达。

Overexpression of c-myb in leukaemic and non-leukaemic variants of cutaneous T-cell lymphoma.

作者信息

Poenitz N, Simon-Ackermann J, Gratchev A, Qadoumi M, Klemke C-D, Stadler R, Kremer A, Radenhausen M, Henke U, Assaf C, Utikal J, Goerdt S, Dippel E

机构信息

Department of Dermatology, Venereology and Allergology, University Medical Centre Mannheim, Ruprecht Karl University of Heidelberg, Mannheim, Germany.

出版信息

Dermatology. 2005;211(2):84-92. doi: 10.1159/000086434.

DOI:10.1159/000086434

PMID:16088151

Abstract

BACKGROUND

The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL).

OBJECTIVE

Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL.

METHODS

c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR.

RESULTS

Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 +/- 0.5) versus MF (1.2 +/- 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 +/- 31,960.32 AU in SS vs. 1,226.35 +/- 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 x 10(-2) +/- 2.27 x 10(-2) in SS vs. 0.91 x 10(-2) +/- 1.18 x 10(-2) in MF vs. 0.24 x 10(-2) +/- 0.11 x 10(-2) in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 x 10(-2) and 10.78 x 10(-2) +/- 7.24 x 10(-2)).

CONCLUSION

Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.

摘要

背景

c-myb癌基因是一种转录因子，通过与在皮肤T细胞淋巴瘤（CTCL）中表达的c-myc或bcl-2等基因的启动子序列结合，调节造血细胞和活化T细胞的增殖、分化和凋亡。

目的

我们进行本研究以评估c-myb表达作为CTCL白血病性和非白血病性变体鉴别诊断的定量参数。

方法

使用免疫组织化学、半定量及定量逆转录聚合酶链反应（RT-PCR）分析21例蕈样肉芽肿（MF）患者、15例塞扎里综合征（SS）患者和15例炎症性皮肤病患者的皮损及外周血中的c-myb表达。

结果

免疫组织化学证实大多数CTCL患者的皮损中有c-myb表达，SS患者（1.86±0.5）的表达倾向高于MF患者（1.2±0.7），而炎症性皮肤病患者的皮损中无c-myb表达。所有SS患者外周血中c-myb均过度表达（100% SS vs. 35.7% MF），表达水平较高（使用半定量RT-PCR时，SS患者为51335.31±31960.32 AU，MF患者为1226.35±1258.29 AU；使用定量RT-PCR时，SS患者为5.72×10⁻²±2.27×10⁻²，MF患者为0.91×10⁻²±1.18×10⁻²，炎症性皮肤病患者为0.24×10⁻²±0.11×10⁻²）。定量RT-PCR显示，SS患者外周血中的CD4⁺细胞及体外细胞系的c-myb表达水平最高（分别为23.27×10⁻²和10.78×10⁻²±7.24×10⁻²）。

结论

c-myb在非白血病性和白血病性CTCL的皮肤病变中均过度表达，且与疾病分期无关，表明其在疾病发展早期起作用。然而，皮损中c-myb表达若为阳性，则是CTCL与炎症性皮肤病鉴别的明确诊断标志物。通过定量RT-PCR评估的外周血中c-myb的高水平表达是SS的一项额外诊断参数，在塞扎里细胞的形态学判定或CD7和CD26的流式细胞术分析结果不明确的病例中可能特别有用。