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Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Targeting of phospho-eIF4E by homoharringtonine eradicates a distinct subset of human acute myeloid leukemia
Hong Zhou1, Rong Zhen Xu2,3, Ying Gu2,3
1Department of Hematology, Hangzhou First People's Hospital, Hangzhou, PR China.
More than half of the patients with acute myeloid leukemia (AML) fail to achieve long-term disease-free survival with current therapies and novel therapeutic strategies are urgently needed. The effects of homoharringtonine (HHT) on the growth of AML cell lines and primary leukemia cells were examined using MTT, colony formation assay. The effects of HHT on both eukaryotic translation initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through western blot and immunofluorescence staining. HHT selectively reduced levels of p-eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and in vivo the growth of a distinct subset of AML cells and primary leukemia cells expressing high level of p-eIF4E through apoptosis. Our findings suggest that HHT might be a first-in-class p-eIF4E-targeted drug and offer a novel therapeutic option for AML patients expressing high level of p-eIF4E.
More than half of the patients with acute myeloid leukemia (AML) fail to achieve long-term disease-free survival with current therapies and novel therapeutic strategies are urgently needed. The effects of homoharringtonine (HHT) on the growth of AML cell lines and primary leukemia cells were examined using MTT, colony formation assay. The effects of HHT on both eukaryotic translation initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through western blot and immunofluorescence staining. HHT selectively reduced levels of p-eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and in vivo the growth of a distinct subset of AML cells and primary leukemia cells expressing high level of p-eIF4E through apoptosis. Our findings suggest that HHT might be a first-in-class p-eIF4E-targeted drug and offer a novel therapeutic option for AML patients expressing high level of p-eIF4E.
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