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Nucleophosmin Gene Mutations Involved in Leukemic Cell Invasion through MMPs
Hui-Yuan Shao, Zong-Yu Miao, Feng-Xian Qin, Xian-Chun Chen, Shi Tan, Hui-Juan Zhang, Ling Zhang*
Key Laboratory of Medical Diagnostics, Ministry of Education, Faculty of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
Abstract: Nucleophosmin (NPM1) mutations have been recently identified as the most frequent genetic alterations in acute myeloid leukemia and played an important role in leukemogenesis. To explore the possible molecular mechanisms of NPM1 mutations in leukemic cell invasion in vitro， the pEGFPC1-NPM1-mA plasmid vector with NPM1 mutation A (NPM1-mA) was transfected into THP-1 cells， and the leukemic cells with stably expressed NPM1-mA protein (THP-1-mA) were established. The expression of MMP-2， MMP-9， TIMP-1 and TIMP-2 was assayed by RT-PCR and Western blot. Compared with the control groups， there was a higher expression of MMP-2 in THP-1-mA group， but a lower expression of MMP-9. At the same time， in THP-1-mA group， the levels of TIMP-2 mRNA and protein were significantly decreased， while the expression of TIMP-1 mRNA and protein was similar to the cells in the control groups. So our findings suggest that MMP-2 and its inhibitor TIMP-2 may play a key role in extramedullary infiltration of leukemic cells with NPM1 mutations.
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