外在信号决定 MN1 白血病中的髓系-红系谱系转换。
Extrinsic signals determine myeloid-erythroid lineage switch in MN1 leukemia.
机构信息
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
出版信息
Exp Hematol. 2010 Mar;38(3):174-9. doi: 10.1016/j.exphem.2010.01.003. Epub 2010 Jan 21.
OBJECTIVE
Transcriptional control of hematopoietic lineage fate relies on the integration of many intra- and extracellular signals. To test whether the microenvironment impacts on leukemic phenotype, we exploited the MN1 model of acute myeloid leukemia under defined genetically modified microenvironmental conditions.
MATERIALS AND METHODS
The requirement of both FLT3 and c-Kit signaling for MN1 leukemias was investigated using retroviral infection of bone marrow cells from wild-type, c-Kit-mutated (W41), and Flt3-ligand knockout cells, and bone marrow transplantation into wild-type, c-Kit-mutated, or Flt3-ligand knockout mice.
RESULTS
Genetic disruption of both FLT3 and c-Kit signaling in the MN1-leukemia model was dispensable for MN1-induced leukemogenesis. However, it induced a switch from myeloid to erythroid phenotype that was preserved, when FLT3 signaling was restored by secondary transplantation of leukemic cells into wild-type recipients.
CONCLUSIONS
Our findings underscore the importance of microenvironmental signals for lineage choice in leukemia and identify signals that are important in myeloid-erythroid lineage decisions.
目的
造血谱系命运的转录控制依赖于许多细胞内和细胞外信号的整合。为了测试微环境是否影响白血病表型，我们利用 MN1 模型在明确的遗传修饰的微环境条件下研究急性髓系白血病。
材料和方法
使用逆转录病毒感染野生型、c-Kit 突变型（W41）和 Flt3 配体敲除细胞的骨髓细胞，并将骨髓移植到野生型、c-Kit 突变型或 Flt3 配体敲除小鼠中，研究 MN1 白血病中 FLT3 和 c-Kit 信号的必需性。
结果
在 MN1 白血病模型中，FLT3 和 c-Kit 信号的遗传破坏对于 MN1 诱导的白血病发生是可有可无的。然而，它诱导了从髓系到红细胞表型的转变，当通过将白血病细胞二次移植到野生型受体中来恢复 FLT3 信号时，这种转变被保留下来。
结论
我们的发现强调了微环境信号对于白血病谱系选择的重要性，并确定了在髓系-红细胞谱系决定中重要的信号。
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