Abstract
Abstract
Differentiation therapy has been successfully applied clinically in cases of acute promyelocytic leukemia (APL), but few differentiation-induction agents other than all-trans retinoic acid (ATRA) have been discovered clinically. Based on our previously reported neuritogenic differentiation activity of synthetic dimeric derivatives of securinine, we explored the leukemia differentiation-induction activity of such as compound, SN3-L6. It was found that SN3-L6 induces transdifferentiation of both acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) cells but unexpectedly, a new transdifferentiation pathway from APL cells to morphologically and immunologically normal megakaryocytes and platelets were discovered. SN3-L6 fails to induce transdifferentiation of ATRA–produced mature granulocytes into megakaryocytes, indicating its selectivity between mature and immature cells. SN3-L6 induces CML K562 cells to transdifferentiate into apoptotic megakaryocytes but without platelet formation, indicating a desirable selectivity between different leukemia cells. Our data illuminate a differentiation gap between AML cells and platelets, and promises applications in leukemia differentiation therapy strategy.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference26 articles.
1. Breitman, T. R., Collins, S. J. & Keene, B. R. Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood 57, 1000–1004 (1981).
2. Huang, M. E. et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72, 567–572 (1988).
3. Huang, M. E. et al. All-trans retinoic acid with or without low dose cytosine arabinoside in acute promyelocytic leukemia. Report of 6 cases. Chin. Med. J. 100, 949–953 (1987).
4. Shen, Z. X. et al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc. Natl Acad. Sci. USA 101, 5328–5335 (2004).
5. Breitman, T. R., Selonic, S. E. & Collins, S. J. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc. Natl Acad. Sci. USA 77, 2936–2940 (1980).
Cited by
17 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献