Analysis of Ikaros family splicing variants in human hematopoietic lineages.
Analysis of Ikaros family splicing variants in human hematopoietic lineages.
复制标题
人类造血谱系中 Ikaros 家族剪接变异的分析。
作者：
M. Matulić;M. Paradžik;B. J. Puškarić;J. Stipić;M. Antica
Ikaros家族的转录因子参与淋巴细胞分化，并在造血途径的特定检查点发挥关键作用。然而，如何发育调控的变化反映在淋巴细胞分化的基因表达程序还没有很好地理解。已经表明，Ikaros家族转录因子的失调与不同人类白血病的发展相关。在这项工作中，我们分析了Ikaros家族成员在不同的白血病细胞中的状态，目的是探索人类造血谱系的转录控制，并为我们理解转录因子在人类白血病中的意义提供一些新的线索。我们采用RT-PCR和特异性引物研究了Ikaros、Aiolos和Helios转录因子及其剪接变体在7个不同类型白血病（ALL、CML、AML）和淋巴瘤（组织细胞性淋巴瘤、Burkitt淋巴瘤和间变性大细胞淋巴瘤）细胞系中的表达。在检查的所有细胞系中，Ikaros以优势Ik 1至Ik 4亚型存在，而小Ik 6亚型不存在。Aiolos以全长Aio 1的形式在B和T来源的大多数细胞系中表达。Helios也只存在于两个长亚型Hel 1和Hel 2中，并且在三分之一的品系中不存在。Aiolos和Helios的阳性和阴性表达在不同类型白血病中的相似分布可能暗示了它们共同的调控途径。
Transcription factors from the Ikaros family are involved in lymphocyte differentiation and have a critical role at specific check points of the haemopoietic pathway. However, how developmentally regulated changes are reflected in gene expression programs of lymphocyte differentiation is not well understood. It has been suggested that disregulation of transcription factors from the Ikaros family is associated with the development of different human leukemias. In this work we analyzed the state of Ikaros family members in different leukemic cells with the aim to explore the transcriptional control of human hematopoietic lineages and shed some new light on our understanding of transcription factor significance in human leukemias. By means of RT-PCR and specific primers we investigated the expression of Ikaros, Aiolos and Helios transcription factors and their splicing variants in seven leukemia cell lines derived from different types of leukemia (ALL, CML, AML) and lymphoma (histiocytic lymphoma, Burkitt lymphoma and anaplastic large cell lymphoma). In all of the cell lines examined Ikaros was present in dominant Ik1 to Ik4 isoforms and small Ik6 isoform was absent. Aiolos was expressed in the majority of the cell lines, of both, B and T origin, in the form of the full length Aio1. Helios was also present only in two long isoforms Hel1 and Hel2, and was absent in one third of the lines. Similar distribution of positive and negative expression of Aiolos and Helios found in various types of leukemias could implicate common pathways of their regulation.