Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia.
Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia.
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DOI：
10.1084/jem.20091071
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发表时间：
2010-11-22
期刊：
影响因子：
--
通讯作者：
Kogan SC
中科院分区：
文献类型：
--
作者：
Jones L;Wei G;Sevcikova S;Phan V;Jain S;Shieh A;Wong JC;Li M;Dubansky J;Maunakea ML;Ochoa R;Zhu G;Tennant TR;Shannon KM;Lowe SW;Le Beau MM;Kogan SC
Myc的致白血病作用驱动急性髓细胞白血病小鼠模型中的复发性三体。8号染色体获得是人类急性髓细胞白血病（AML）中最常见的染色体获得。有人假设MYC原癌基因的获得在8三体中具有核心重要性，但支持这一点的实验数据有限且有争议。在MRP 8启动子驱动PML-RARA融合基因在骨髓细胞中表达的早幼粒细胞白血病小鼠模型中，由于小鼠15号染色体的三体性，在大约三分之二的病例中获得Myc等位基因。我们使用该模型来检验MYC是AML中获得三体的基础的想法。我们使用逆转录病毒载体来驱动表达PML-RARA转基因的骨髓中的野生型、高形态或低形态MYC的表达。MYC逆转录病毒在髓系白血病发生中起协同作用，并抑制15号染色体的获得。当PML-RARA转基因在Myc单倍体不足的背景下表达时，我们观察到伴随白血病转化的野生型Myc等位基因拷贝增加的选择。此外，我们发现，人类髓性白血病与三体8有增加MYC。这些数据表明，MYC的获得可有助于人类AML的最常见的三体性的致病作用。
The leukemogenic effects of Myc drive recurrent trisomy in a mouse model of acute myeloid leukemia. Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia (AML). It has been hypothesized that gain of the MYC protooncogene is of central importance in trisomy 8, but the experimental data to support this are limited and controversial. In a mouse model of promyelocytic leukemia in which the MRP8 promoter drives expression of the PML-RARA fusion gene in myeloid cells, a Myc allele is gained in approximately two-thirds of cases as a result of trisomy for mouse chromosome 15. We used this model to test the idea that MYC underlies acquisition of trisomy in AML. We used a retroviral vector to drive expression of wild-type, hypermorphic, or hypomorphic MYC in bone marrow that expressed the PML-RARA transgene. MYC retroviruses cooperated in myeloid leukemogenesis and suppressed gain of chromosome 15. When the PML-RARA transgene was expressed in a Myc haploinsufficient background, we observed selection for increased copies of the wild-type Myc allele concomitant with leukemic transformation. In addition, we found that human myeloid leukemias with trisomy 8 have increased MYC. These data show that gain of MYC can contribute to the pathogenic effect of the most common trisomy of human AML.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.4
作者：
KARASUYAMA, H;MELCHERS, F
通讯作者：
MELCHERS, F
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
20.3
作者：
Kottaridis, PD;Gale, RE;Linch, DC
通讯作者：
Linch, DC
影响因子：
20.3
作者：
Jin, Guang;Yamazaki, Yukari;Nakamura, Takuro
通讯作者：
Nakamura, Takuro