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.

在急性早幼粒细胞白血病（APL）的病例中，分化疗法已在临床上成功应用，但临床上除全反式维甲酸（ATRA）以外几乎没有发现分化诱导剂。基于我们先前报道的蛇麻碱合成二聚体衍生物的神经原性分化活性，我们探索了化合物SN3-L6的白血病分化诱导活性。已发现SN3-L6诱导急性髓性白血病（AML）和慢性粒细胞性白血病（CML）细胞的转分化，但出乎意料的是，发现了从APL细胞到形态和免疫学上正常的巨核细胞和血小板的新转分化途径。SN3-L6未能诱导ATRA产生的成熟粒细胞向巨核细胞的转分化，表明其在成熟细胞和未成熟细胞之间的选择性。SN3-L6诱导CML K562细胞转分化为凋亡的巨核细胞，但没有血小板形成，表明不同白血病细胞之间具有理想的选择性。我们的数据阐明了AML细胞与血小板之间的分化差距，并有望在白血病分化治疗策略中得到应用。