Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal, Montréal, QC, Canada.
Blood. 2011 Feb 10;117(6):1899-910. doi: 10.1182/blood-2010-10-311001. Epub 2010 Dec 6.
The Graffi murine leukemia virus induces a large spectrum of leukemias in mice and thus provides a good model to compare the transcriptome of all types of leukemias. We analyzed the gene expression profiles of both T and B leukemias induced by the virus with DNA microarrays. Given that we considered that a 4-fold change in expression level was significant, 388 probe sets were associated to B, to T, or common to both leukemias. Several of them were not yet associated with lymphoid leukemia. We confirmed specific deregulation of Fmn2, Arntl2, Bfsp2, Gfra2, Gpm6a, and Gpm6b in B leukemia, of Nln, Fbln1, and Bmp7 in T leukemias, and of Etv5 in both leukemias. More importantly, we show that the mouse Fmn2 induced an anchorage-independent growth, a drastic modification in cell shape with a concomitant disruption of the actin cytoskeleton. Interestingly, we found that human FMN2 is overexpressed in approximately 95% of pre-B acute lymphoblastic leukemia with the highest expression levels in patients with a TEL/AML1 rearrangement. These results, surely related to the role of FMN2 in meiotic spindle maintenance, suggest its important role in leukemogenesis. Finally, we propose a new panel of genes potentially involved in T and/or B leukemias.
The Graffi 鼠白血病病毒可在小鼠中诱导广泛的白血病谱，因此为比较各种白血病的转录组提供了良好的模型。我们使用 DNA 微阵列分析了病毒诱导的 T 细胞和 B 细胞白血病的基因表达谱。考虑到我们认为表达水平变化 4 倍是显著的，因此与 B 细胞白血病、T 细胞白血病或两者都相关的探针集有 388 个。其中有几个尚未与淋巴细胞白血病相关。我们证实了 B 白血病中 Fmn2、Arntl2、Bfsp2、Gfra2、Gpm6a 和 Gpm6b 的特异性下调，T 白血病中 Nln、Fbln1 和 Bmp7 的特异性下调，以及两种白血病中 Etv5 的特异性下调。更重要的是，我们表明，小鼠 Fmn2 可诱导非锚定依赖性生长，细胞形态发生剧烈变化，同时破坏肌动蛋白细胞骨架。有趣的是，我们发现人类 FMN2 在约 95%的前 B 急性淋巴细胞白血病中过度表达，在 TEL/AML1 重排的患者中表达水平最高。这些结果与 FMN2 在减数分裂纺锤体维持中的作用有关，表明其在白血病发生中的重要作用。最后，我们提出了一个新的潜在涉及 T 和/或 B 白血病的基因表达谱。
