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

• Published in: Blood cancer journal (New York) Vol. 5; no. 8; p. e339
• Main Authors: Chen, C-C, You, J-Y, Gau, J-P, Huang, C-E, Chen, Y-Y, Tsai, Y-H, Chou, H-J, Lung, J, Yang, M-H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-08-2015; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/109; 13/31; 38/77; 38/89; 631/67; 631/67/1990/283/1897; 82/80; Antineoplastic Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Bone Marrow; Cancer Research; Cell Line; Cytarabine - therapeutic use; Epithelial-Mesenchymal Transition; Hematology; Humans; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncology; Original; original-article; Polycomb Repressive Complex 1 - metabolism; Prognosis; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/bcj.2015.67

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 that, in a subset of AML patients,
Twist1
has a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes.