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Overexpression of HOXB7 and homeobox genes characterizes multiple myeloma patients lacking the major primary immunoglobulin heavy chain locus translocations

机译:HOXB7和同源盒基因的过表达表征缺乏主要主要免疫球蛋白重链基因座易位的多发性骨髓瘤患者

摘要

Homeobox (HOX) gene transcription factors are frequently deregulated in hematologic malignancies and involved in leukemogenic transformation [1]. Moreover, their overexpression has been associated with tumoral-induced neoangiogenesis in solid cancer [2]. The expression and the role of these genes have not yet been completely elucidated in multiple myeloma (MM). Recently, we reported that a small fraction of MM patients shows a HOXB7 overexpression as compared with normal samples and that HOXB7 expression correlates with bone marrow angiogenesis and the production of the proangiogenic factors by MM cells [3]. Other authors previously reported that HOXA cluster genes are expressed in a small fraction of MM patients [4]. Herein, we extended our previous evidences with the evaluation of the expression level of HOXB7 and the other gene family members in a large number of primary MM cells in relationship with the different molecular subgroups of MM and the presence of specific chromosome translocations. We found that HOXB7 and other genes of HOX family have a preferential distribution based on the characteristics of molecular MM subtypes based on the translocations/cyclins (TC) classification, suggesting a potential relationship between HOX genes expression, angiogenesis, and molecular features of MM patients.
机译:同源异型框(HOX)基因转录因子在血液系统恶性肿瘤中经常失调,并参与致白血病转化[1]。而且,它们的过表达与实体癌中肿瘤诱导的新血管生成有关[2]。这些基因的表达和作用尚未在多发性骨髓瘤(MM)中得到完全阐明。最近,我们报道了一小部分MM患者与正常样品相比显示HOXB7过表达,并且HOXB7的表达与MM细胞的骨髓血管生成和促血管生成因子的产生相关[3]。其他作者以前曾报道过HOXA簇基因在一小部分MM患者中表达[4]。在本文中,我们通过评估与大量不同的MM分子亚群相关的大量原代MM细胞中HOXB7和其他基因家族成员的表达水平,以及存在特定的染色体易位,来扩展先前的证据。我们发现HOXB7和HOX家族的其他基因基于分子MM亚型的特征(基于易位/细胞周期蛋白(TC)分类)具有优先分布,表明HOX基因表达,血管生成和MM患者的分子特征之间存在潜在关系。

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