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JunB is a gatekeeper for B-lymphoid leukemia

机译：JunB是B淋巴白血病的看门人

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Loss of JunB has been observed in human leukemia and lymphoma, but it remains unknown, whether this loss is relevant to disease progression. Here, we investigated the consequences of JunB deficiency using Abelson-induced B-lymphoid leukemia as a model system. Mice deficient in JunB expression succumbed to Abelson-induced leukemia with increased incidence and significantly reduced latency. Similarly, bcr/abl p185-transformed JunB-deficient (junB/) cells induced leukemia in RAG2-/- mice displaying a more malignant phenotype. These observations indicated that cell intrinsic effects within the junB/ tumor cells accounted for the accelerated leukemia development. Indeed, explantated bcr/abl p185 transformed junB/ cells proliferated faster than the control cells. The proliferative advantage emerged slowly after the initial transformation process and was associated with increased expression levels of the cell cycle kinase cdk6 and with decreased levels of the cell cycle inhibitor p16INK4a. These alterations were due to irreversible reprogramming of the cell, because – once established – accelerated disease induced by junB/ cells was not reverted by re-introducing JunB. Consistent with this observation, we found that the p16 promoter was methylated. Thus, JunB functions as a gatekeeper during tumor evolution. In its absence, transformed leukemic cells acquire an enhanced proliferative capacity, which presages a more malignant disease.
机译：在人类白血病和淋巴瘤中已观察到JunB的缺失，但这种缺失是否与疾病进展有关尚不清楚。在这里，我们调查了使用Abelson诱导的B淋巴白血病作为模型系统的JunB缺乏症的后果。 JunB表达缺陷的小鼠死于Abelson诱导的白血病，发病率增加且潜伏期大大缩短。同样，bcr / abl p185转化的JunB缺陷（junB /）细胞在显示出更恶性表型的RAG2-/-小鼠中诱导白血病。这些观察结果表明，junB /肿瘤细胞内的细胞内在作用是加速白血病发展的原因。实际上，外植的bcr / abl p185转化的junB /细胞的增殖速度快于对照细胞。在最初的转化过程后，增殖优势逐渐显现，并与细胞周期激酶cdk6的表达水平升高和细胞周期抑制剂p16INK4a的水平降低有关。这些改变归因于细胞的不可逆重编程，因为一旦建立，由junB /细胞诱导的加速疾病就不会通过重新引入JunB而得以逆转。与该观察结果一致，我们发现p16启动子被甲基化。因此，JunB在肿瘤进化过程中起着关守的作用。在没有它的情况下，转化的白血病细胞获得增强的增殖能力，从而预示着更恶性的疾病。

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