Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12)

被引:114
作者
Kuno, Y [1 ]
Abe, A [1 ]
Emi, N [1 ]
Iida, M [1 ]
Yokozawa, T [1 ]
Towatari, M [1 ]
Tanimoto, M [1 ]
Saito, H [1 ]
机构
[1] Nagoya Univ, Sch Med, Dept Internal Med 1, Showa Ku, Nagoya, Aichi 4668550, Japan
关键词
D O I
10.1182/blood.V97.4.1050
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The TEL gene on 12p12-13 is a target for a number of translocations associated with various hematological malignancies. The fusion of the TEL gene to the Syk gene in a patient with myelodysplastic syndrome (MDS) with t(9;12)(q22;p12) is reported. Southern blot analysis of patient bone marrow cells with TEL and Syk gene probes detected rearranged fragments. Anchored polymerase chain reaction identified the Syk gene, a nonreceptor tyrosine kinase, on 9q22 fused downstream of TEL exon 5, The TEL gene was fused in-frame to Syk and produced a fusion protein that was constitutively phosphorylated in tyrosine with dimerization that was mediated by the helix-loop-helix domain of TEL. A TEL-Syk fusion product transformed the murine hematopoietic cell line BaF3 to interleukin-3 growth factor independence. TEL-Syk is a novel transforming protein and leads to the transformation of hematopoietic cells. These data implicate that the rearranged Syk gene is involved in the pathogenesis of hematopoietic malignancies. (C) 2001 by The American Society of Hematology.
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页码:1050 / 1055
页数:6
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