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

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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.