Analysis of the mechanism of L-asparaginase to suppress the highly expressed eIF4E in NK-cell lymphoma

我们已经展示了L-天冬酰胺酶（L-ASP）的两种新机制，即使对化疗耐药的NK细胞淋巴瘤也有效。首先，L-ASP降低了包括eIF 4 E在内的各种翻译起始因子的表达水平，这反过来又抑制了MYC、BCL-2和eIF 4 E本身的翻译，具有促肿瘤和抑制凋亡活性。第二，L-ASP耗尽谷氨酰胺，导致TCA循环耗尽和不足，最终导致细胞凋亡。结果表明，谷氨酰胺成瘾的各种淋巴系统恶性肿瘤，包括急性淋巴细胞白血病和TCA循环在抑制细胞凋亡的中心作用。

We have shown two new mechanism of L-asparaginase(L-ASP), which is efficient even for chemotherapy-resistant NK-cell lymphoma. First, L-ASP decreased expression levels of various translation initiation factors including eIF4E, which in turn suppressed the translation of MYC, BCL-2 and eIF4E itself with tumor promoting and apoptosis inhibiting activities. Second, L-ASP depleted glutamine, induced TCA cycle depletion and insufficiency, and finally caused apoptosis. The result showed glutamine addiction of various lymphoid malignancies including acute lymphoblastic leukemia and the central role of TCA cycle in the suppression of apoptosis.