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Cell Death Discovery

Cell Death Discovery

IF: 6.1
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Induction of differentiation of the acute myeloid leukemia cell line (HL-60) by a securinine dimer

Published:12 November 2020 DOI: 10.1038/s41420-020-00354-3 PMID: 33298839
Wen Hou, Zhen-Ya Wang, Jing Lin, Wei-Min Chen

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.

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AT9283 896466-04-9 C19H23N7O2 139 suppliers $43.00-$4365.90
AT9283 896466-04-9 C19H23N7O2 139 suppliers $43.00-$4365.90
AT9283 896466-04-9 C19H23N7O2 139 suppliers $43.00-$4365.90

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