Bijl J J, Rieger E, van Oostveen J W, Walboomers J M, Kreike M, Willemze R, Meijer C J
Department of Pathology, Vrije Universiteit Hospital, Amsterdam, The Netherlands.
Am J Pathol. 1997 Oct;151(4):1067-74.
Homeobox (HOX) genes are involved in the lineage-specific differentiation of bone marrow stem cells. Recently, we reported a largely similar expression pattern of HOXC4 and HOXC6 in normal and neoplastic cells of the lymphoid lineage. In contrast, HOXC5 was specifically expressed in a subset of B-cell non-Hodgkin's lymphomas (B-NHL) but not in normal lymphocytes or lymphoid leukemias. This might suggest a role for HOXC5 in the pathogenesis of these lymphomas. In the present study the expression of HOXC4, HOXC5, and HOXC6 in primary cutaneous lymphomas was investigated. Using RNA in situ hybridization (RISH) and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), we found strong expression of HOXC4 and HOXC6 in all, except one, primary cutaneous lymphomas and all reactive cutaneous lymphoid infiltrates. Interestingly, a strong expression of HOXC5 in primary anaplastic CD30+ large T-cell lymphomas was found. RISH was consistently negative for HOXC5 in all other types of primary cutaneous B- and T-cell lymphomas. However, by semiquantitative RT-PCR these lymphomas showed a weak expression of HOXC5 mRNA. Therefore, we concluded that these lymphomas express low constitutive levels of HOXC5 mRNA. Furthermore, HOXC5 expression was consistently absent in reactive cutaneous lymphoid infiltrates, hyperplastic tonsils and lymph nodes, and peripheral blood lymphocytes either unstimulated or stimulated by a cocktail of CD3 and CD28 antibodies. As a strong expression of HOXC5 in primary cutaneous lymphomas was observed only in anaplastic large T-cell lymphomas and reactive control tissues lacked HOXC5 expression, these data strongly support a role for HOXC5 in the genesis of anaplastic large-T-cell lymphomas.
同源框（HOX）基因参与骨髓干细胞的谱系特异性分化。最近，我们报道了HOXC4和HOXC6在淋巴谱系的正常细胞和肿瘤细胞中表达模式大体相似。相比之下，HOXC5在一部分B细胞非霍奇金淋巴瘤（B-NHL）中特异性表达，但在正常淋巴细胞或淋巴白血病中不表达。这可能提示HOXC5在这些淋巴瘤的发病机制中起作用。在本研究中，我们调查了HOXC4、HOXC5和HOXC6在原发性皮肤淋巴瘤中的表达。使用RNA原位杂交（RISH）和半定量逆转录聚合酶链反应（RT-PCR），我们发现除1例原发性皮肤淋巴瘤外，所有原发性皮肤淋巴瘤和所有反应性皮肤淋巴浸润中HOXC4和HOXC6均有强表达。有趣的是发现原发性间变性CD30+大T细胞淋巴瘤中HOXC5有强表达。在所有其他类型的原发性皮肤B细胞和T细胞淋巴瘤中，RISH检测HOXC5始终为阴性。然而，通过半定量RT-PCR，这些淋巴瘤显示HOXC5 mRNA有弱表达。因此，我们得出结论，这些淋巴瘤表达低水平组成性HOXC5 mRNA。此外，在反应性皮肤淋巴浸润、增生性扁桃体和淋巴结以及未受刺激或经CD3和CD28抗体混合物刺激的外周血淋巴细胞中，始终未检测到HOXC5表达。由于仅在间变性大T细胞淋巴瘤中观察到原发性皮肤淋巴瘤中HOXC5有强表达，且反应性对照组织中缺乏HOXC5表达，这些数据有力支持HOXC5在间变性大T细胞淋巴瘤发生中起作用。
