Cuenco Grace M, Ren Ruibao
Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02454-9110, USA.
Oncogene. 2004 Jan 15;23(2):569-79. doi: 10.1038/sj.onc.1207143.
We have previously shown that BCR/ABL, a fusion protein generated by the t(9;22)(q34;q11) translocation found in the vast majority of chronic myelogenous leukemia (CML), cooperates with AML1/MDS1/EVI1 (AME), a fusion transcription factor generated by a t(3;21)(q26;q22) translocation identified as a secondary mutation in some cases of CML during the blast phase (CML-BC), in the rapid induction of an acute myelogenous leukemia (AML) in mice. In this study, we evaluated the leukemogenic potential of EVI1-, MDS1/EVI1- and AML1-related oncoproteins (AML1Delta, AML1/MDS1). We found that ectopic expression of either EVI1 or MDS1/EVI1 impaired hematopoiesis. However, neither EVI1 nor MDS1/EVI1 was sufficient for inducing AML in mice, although EVI1 did induce some hematologic neoplasia other than AML with a low efficiency. In addition, unlike AME, none of the EVI1- or AML1-related oncoproteins examined were capable of fully cooperating with BCR/ABL in the induction of AML. The results indicate that both the AML1 and EVI1 oncogenic components are required for the leukemogenic potential of AME and for the cooperation of AME and BCR/ABL in the induction of AML.
我们之前已经表明，BCR/ABL是一种由t(9;22)(q34;q11)易位产生的融合蛋白，在绝大多数慢性髓性白血病（CML）中均可发现，它与AML1/MDS1/EVI1（AME）协同作用，AME是一种由t(3;21)(q26;q22)易位产生的融合转录因子，在某些CML急变期（CML-BC）病例中被鉴定为二次突变，二者可在小鼠中快速诱导急性髓性白血病（AML）。在本研究中，我们评估了EVI1、MDS1/EVI1和AML1相关癌蛋白（AML1Delta、AML1/MDS1）的致白血病潜力。我们发现，EVI1或MDS1/EVI1的异位表达均损害造血功能。然而，EVI1和MDS1/EVI1均不足以在小鼠中诱导AML，尽管EVI1确实以低效率诱导了一些除AML之外的血液肿瘤。此外，与AME不同，所检测的EVI1或AML1相关癌蛋白均不能在AML诱导过程中与BCR/ABL充分协同作用。结果表明，AML1和EVI1致癌成分对于AME的致白血病潜力以及AME与BCR/ABL在AML诱导中的协同作用均是必需的。
