Schwieger Maike, Löhler Jürgen, Friel Jutta, Scheller Marina, Horak Ivan, Stocking Carol
Department of Cell and Virus Genetics, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, D-20251 Hamburg, Germany.
J Exp Med. 2002 Nov 4;196(9):1227-40. doi: 10.1084/jem.20020824.
The translocation (8;21), generating the AML1-ETO fusion protein, is one of the most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML). To elucidate its role in oncogenesis, bone marrow (BM) cells were infected with a retroviral vector carrying AML1-ETO and transplanted into mice. In contrast to previous transgenic mouse models, we show that AML1-ETO directly stimulates granulopoiesis, suppresses erythropoiesis, and impairs the maturation of myeloid, B, and T lymphoid cells in vivo. To determine the significance of earlier findings that expression of the tumor suppressor ICSBP is often downregulated in AML myeloblasts, AML1-ETO was introduced into BM cells derived from mice lacking the interferon regulatory factor ICSBP. Our findings demonstrate that AML1-ETO synergizes with an ICSBP deficiency to induce myeloblastic transformation in the BM, reminiscent of AML.
导致AML1-ETO融合蛋白产生的8号与21号染色体易位，是与急性髓系白血病（AML）相关的最常见染色体异常之一。为阐明其在肿瘤发生中的作用，用携带AML1-ETO的逆转录病毒载体感染骨髓（BM）细胞，并将其移植到小鼠体内。与先前的转基因小鼠模型不同，我们发现AML1-ETO在体内直接刺激粒细胞生成，抑制红细胞生成，并损害髓系、B淋巴细胞和T淋巴细胞的成熟。为确定早期研究结果的意义，即肿瘤抑制因子ICSBP在AML成髓细胞中的表达常下调，将AML1-ETO导入缺乏干扰素调节因子ICSBP的小鼠来源的BM细胞中。我们的研究结果表明，AML1-ETO与ICSBP缺陷协同作用，在BM中诱导成髓细胞转化，这与AML相似。
