2016
DOI: 10.1038/leu.2016.270
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Nuclear FOXM1 drives chemoresistance in AML

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Cited by 25 publications
(23 citation statements)
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“…We hypothesized that the improved outcomes in this subset of NPM1 mut AML are associated with the cytoplasmic localization and consequent inactivation of oncogenic transcription factor FOXM1. To prove this notion, we demonstrated predominantly cytoplasmic localization of FOXM1 and NPM only in AML primary patient samples with NPM1 mutations (11). In addition, we investigated the effects of nuclear FOXM1 on chemoresistance to cytosine arabinoside (cytarabine), the backbone of AML chemotherapy and we found that stable knockdown of FOXM1 in AML cell lines with nuclear FOXM1 resulted in increased sensitivity to this chemotherapeutic agent (11).…”
Section: Interaction Between Npm and Foxm1 Is Required For Foxm1 Ementioning
confidence: 87%
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“…We hypothesized that the improved outcomes in this subset of NPM1 mut AML are associated with the cytoplasmic localization and consequent inactivation of oncogenic transcription factor FOXM1. To prove this notion, we demonstrated predominantly cytoplasmic localization of FOXM1 and NPM only in AML primary patient samples with NPM1 mutations (11). In addition, we investigated the effects of nuclear FOXM1 on chemoresistance to cytosine arabinoside (cytarabine), the backbone of AML chemotherapy and we found that stable knockdown of FOXM1 in AML cell lines with nuclear FOXM1 resulted in increased sensitivity to this chemotherapeutic agent (11).…”
Section: Interaction Between Npm and Foxm1 Is Required For Foxm1 Ementioning
confidence: 87%
“…Overall, in cancer cells NPM interacts with FOXM1 and their interaction is required for sustaining the level and localization of FOXM1 (5). In AML cells mutant NPM drives FOXM1 to the cytoplasm leading to its inactivation (11). Generally speaking, interaction of nuclear FOXM1 with NPM may be targeted by peptides or small molecules in human cancer.…”
Section: Interaction Between Npm and Foxm1 Is Required For Foxm1 Ementioning
confidence: 99%
“…Inhibition of FOXM1 reduced proliferation in AML leukemia cell lines 27 . In addition, FOXM1 was reported to contribute to chemoresistance in AML, although the molecular mechanisms have not been determined 28,29 . These studies point to the importance of further understanding the role and underlying molecular mechanisms of FOXM1 in LSCs in AML.…”
mentioning
confidence: 99%
“…Having established the role of FOXM1 in mediating chemotherapy resistance in myeloid neoplasms, we went on to inhibit this transcription factor. First, leukemia cell lines with stable knockdown of FOXM1 were generated as previously published ( 27 ). Using methycellulose-based colony assays, we noted a dramatic decrease in colony size and numbers in KG-1 ( Figure 3, A and B ) and MV-4-11 cell lines with knockdown of FOXM1 ( Supplemental Figure 3, A and B ), suggesting an important role for FOXM1 in the colony-forming activity of AML cells.…”
Section: Resultsmentioning
confidence: 99%