Bernardin Florence, Yang Yandan, Cleaves Rebecca, Zahurak Marianna, Cheng Linzhao, Civin Curt I, Friedman Alan D
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Cancer Res. 2002 Jul 15;62(14):3904-8.
TEL-AML1 is expressed from the t(12;21) chromosomal translocation inB-precursor acute lymphocytic leukemia (ALL). Creation of the TEL-AML1fusion disrupts one copy of the TEL and AML1 genes, and loss of TEL or AML1 is also associated with cases of acute leukemia without TEL-AML1. To determine whether TEL-AML1 can contribute to leukemogenesis, we transduced marrow from C57BL/6 mice with a retroviral vector expressing TEL-AML1 or with a control vector. Transduced cells were introduced into irradiated syngeneic recipients. Two of 9 TEL-AML1 mice developed ALL (one T-lineage ALL and one B-precursor ALL), whereas 0 of 20 control mice developed leukemia. The B-precursor ALL was retransplantable and expressed TEL-AML1. We similarly transduced marrow from C57BL/6 mice lacking the overlapping p16(INK4a)p19(ARF) genes and transplanted the cells into wild-type recipients. No control mice died, but six of eight TEL-AML1/p16p19 mice died with leukemia. Overall, these findings indicate that TEL-AML1 contributes to leukemogenesis and may cooperate with loss of p16(INK4a)p14(ARF) to transform lymphoid progenitors.
TEL-AML1由B前体急性淋巴细胞白血病（ALL）中的t(12;21)染色体易位表达。TEL-AML1融合基因的产生破坏了TEL和AML1基因的一个拷贝，并且TEL或AML1的缺失也与无TEL-AML1的急性白血病病例相关。为了确定TEL-AML1是否有助于白血病发生，我们用表达TEL-AML1的逆转录病毒载体或对照载体转导C57BL/6小鼠的骨髓。将转导的细胞引入经照射的同基因受体。9只TEL-AML1小鼠中有2只发生了ALL（1只T系ALL和1只B前体ALL），而20只对照小鼠中无1只发生白血病。该B前体ALL可再次移植并表达TEL-AML1。我们同样转导了缺乏重叠的p16(INK4a)p19(ARF)基因的C57BL/6小鼠的骨髓，并将细胞移植到野生型受体中。对照小鼠无一死亡，但8只TEL-AML1/p16p19小鼠中有6只死于白血病。总体而言，这些发现表明TEL-AML1有助于白血病发生，并且可能与p16(INK4a)p14(ARF)缺失协同作用以转化淋巴祖细胞。
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