培养的白血病和淋巴瘤细胞中Notch信号转导的差异调节

Differential regulation of Notch signal transduction in leukaemia and lymphoma cells in culture.

作者信息

Chiaramonte Raffaella, Calzavara Elisabetta, Balordi Francesca, Sabbadini Marta, Capello Daniela, Gaidano Gianluca, Serra Anna, Comi Paola, Sherbet G V

机构信息

Department of Biomedical Sciences and Technologies, University of Milano, LITA-via Fratelli Cervi 93-20090 Segrate (MI), Italy.

出版信息

J Cell Biochem. 2003 Feb 15;88(3):569-77. doi: 10.1002/jcb.10383.

DOI:10.1002/jcb.10383

PMID:12532332

Abstract

The transduction of Notch signal plays an intricate role in cell differentiation and pathogenesis of haematological malignancies as well as in certain congenital conditions. We found no genomic changes in either gene in 34 leukaemic samples and 25 leukaemia and lymphoma cell lines. The functionality of Notch signalling was tested using HES1 gene activation. We show that Notch signalling is differentially regulated in T-acute lymphoblastic leukaemia (ALL) and B-lymphoma cells. The Notch pathway is intact in a majority of B-lymphoma cell lines, but EBNA2, which mimics notch function, can occasionally activate the pathway. In contrast, the Notch pathway is constitutively active in T-ALL. This is the first demonstration of a distinction between B-lymphomas and T-cell leukaemias in the functioning of the Notch-signalling pathway. This might be related to their pathogenesis.

摘要

Notch信号转导在细胞分化、血液系统恶性肿瘤的发病机制以及某些先天性疾病中发挥着复杂的作用。我们在34例白血病样本以及25株白血病和淋巴瘤细胞系中均未发现这两个基因的基因组改变。使用HES1基因激活来测试Notch信号的功能。我们发现，Notch信号在T细胞急性淋巴细胞白血病（ALL）和B淋巴瘤细胞中受到不同的调控。在大多数B淋巴瘤细胞系中，Notch信号通路是完整的，但模拟Notch功能的EBNA2偶尔可激活该通路。相比之下，Notch信号通路在T-ALL中呈组成性激活。这是首次证明Notch信号通路在B淋巴瘤和T细胞白血病功能上存在差异。这可能与它们的发病机制有关。