Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia

Blood Cancer Journal
C-C ChenM-H Yang

Abstract

Epithelial-mesenchymal transition (EMT) is a critical process for inducing stem-like properties of epithelial cancer cells. However, the role of EMT inducers in hematological malignancies is unknown. Twist1, an EMT inducer necessary for cell migration, has recently been found to have transcriptionally regulatory activity on the expression of Bmi1, and these two are capable of promoting tumorigenesis in a synergized manner. Knowing that Bmi1 expression is essential for maintenance of leukemic stem cells, we speculate that Twist1 might govern the pathogenesis of acute myeloid leukemia (AML) development as well. We found that upregulated Twist1 increased Bmi1 expression in AML and endued leukemic cells a higher proliferative potential and increased resistance to apoptosis. In primary AML samples, there was strong positive correlation between the expression levels of Twist1 and Bmi1. AML patients whose leukemic blasts harbored overexpressed Twist1 had a more aggressive clinical phenotype, but they were more likely to have a better clinical outcome after standard therapy. In vitro studies confirmed that Twist1-overexpressing leukemic cells were more susceptible to cytarabine, but not daunorubicin, cytotoxicity. Our findings suggest ...Continue Reading

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Citations

Jun 30, 2016·International Journal of Molecular Sciences·Lisa PleyerRichard Greil
Nov 22, 2019·The Oncologist·Jacob J AdashekRazelle Kurzrock
Oct 21, 2016·American Journal of Hematology·Alexandros MakisErsi Voskaridou
Apr 25, 2018·Journal of Biomedical Science·San-Chi ChenMuh-Hwa Yang
Jun 27, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jian LinJie Xu
Oct 19, 2021·Frontiers in Cell and Developmental Biology·Tendai HunyenyiwaAkiko Mammoto

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Methods Mentioned

BETA
transfection
fluorescence-activated cell sorter
dissection

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