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15‐Methylene‐Eburnamonine Kills Leukemic Stem Cells and Reduces Engraftment in a Humanized Bone Marrow Xenograft Mouse Model of Leukemia
Author(s) -
Gunasekara Dilini C.,
Zheng Mary M.,
Mojtahed Tara,
Woods James R.,
Fandy Tamer E.,
Riofski Mark V.,
Glackin Carlotta A.,
Hassan Hazem E.,
Kirshner Julia,
Colby David A.
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600334
Subject(s) - leukemia , cancer research , bone marrow , stem cell , cytotoxic t cell , chronic myelogenous leukemia , progenitor cell , chronic lymphocytic leukemia , immunology , medicine , biology , in vitro , microbiology and biotechnology , biochemistry
Recent studies suggest that leukemia stem cells (LSCs) play a critical role in the initiation, propagation, and relapse of leukemia. Herein we show that (−)‐15‐methylene‐eburnamonine, a derivative of the alkaloid (−)‐eburnamonine, is cytotoxic against acute and chronic lymphocytic leukemias (ALL and CLL) and acute myelogenous leukemia (AML). The agent also decreases primary LSC frequency in vitro. The cytotoxic effects appear to be mediated via the oxidative stress pathways. Furthermore, we show that the compound kills AML, ALL, and CLL stem cells. By the use of a novel humanized bone marrow murine model of leukemia (huBM/NSG), it was found to decrease progenitor cell engraftment.