Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32)
Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32)
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DOI：
10.1182/blood-2004-12-4897
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发表时间：
2005-06-15
期刊：
影响因子：
20.3
通讯作者：
Cools, J
中科院分区：
文献类型：
--
作者：
De Keersmaecker, K;Graux, C;Cools, J
BCR-ABL1融合激酶常与慢性髓性白血病和b细胞急性淋巴母细胞白血病相关，但在t细胞急性淋巴母细胞白血病（T-ALL）中罕见。我们最近在6%的T-ALL患者中发现NUP214-ABL1是ABL1融合基因的变体。在这里，我们描述了另一种ABL1融合的鉴定，EML1ABL1，在t - all患者中，隐性t(9;14)（q34;q32）与CDKN2A （p16）的缺失和TLX1 （HOX11）的表达相关。棘皮微管相关蛋白样1- abelson 1 （EML1-ABL1）是一种组成性磷酸化酪氨酸激酶，通过激活细胞外信号相关激酶1/2 （Erk1/2）、信号转导和转录激活因子5 （Stat5）和Lyn激酶等存活和增殖途径，将Ba/F3细胞转化为生长因子独立的生长。EML1的螺旋结构域的缺失取消了融合激酶的转化特性。EML1-ABL1和断点簇区(BCR)-ABL1对酪氨酸激酶抑制剂伊马替尼同样敏感。这些数据进一步证明了ABL1融合参与T-ALL的发病机制，并确定EMLI-ABL1是伊马替尼的一个新的治疗靶点。(c) 2005年由美国血液学会出版。
The BCR-ABL1 fusion kinase is frequently associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia but is rare in T-cell acute lymphoblastic leukemia (T-ALL). We recently identified NUP214-ABL1 as a variant ABL1 fusion gene in 6% of T-ALL patients. Here we describe the identification of another ABL1 fusion, EML1ABL1, in a T-ALL patient with a cryptic t(9;14)(q34;q32) associated with deletion of CDKN2A (p16) and expression of TLX1 (HOX11). Echinoderm microtubule-associated protein-like 1-Abelson 1 (EML1-ABL1) is a constitutively phosphorylated tyrosine kinase that transforms Ba/F3 cells to growth factor-independent growth through activation of survival and proliferation pathways, including extracellular signal-related kinase 1/2 (Erk1/2), signal transducers and activators of transcription 5 (Stat5), and Lyn kinase. Deletion of the coiled-coil domain of EML1 abrogated the transforming properties of the fusion kinase. EML1-ABL1 and breakpoint cluster region (BCR)-ABL1 were equally sensitive to the tyrosine kinase inhibitor imatinib. These data further demonstrate the involvement of ABL1 fusions in the pathogenesis of T-ALL and identify EMLI-ABL1 as a novel therapeutic target of imatinib. (c) 2005 by The American Society of Hematology.