Twist as a new prognostic marker in hematological malignancies

Abstract

Twist proteins are members of basic helix-loop-helix family and are major regulators of embryogenesis. In adult humans, Twist proteins are mainly expressed in precursor cells, including myogenic, osteoblastic, chondroblastic and myelomonocytic lineages, maintaining their undifferentiated state. In addition, they play important roles in lymphocyte function and maturation. Recently, several studies have reported regulatory roles for Twist in the function and development of hematopoietic cells as well as in survival and development of numerous hematological malignancies. It is activated by numerous signal transduction pathways, including Akt, nuclear factor κB, Wnt, signal transducer and activator of transcription 3, mitogen-activated protein kinase and Ras signaling. Activated Twist has an anti-apoptotic role and protects cancer cells from apoptotic cell death. In addition, overexpression of Twist promotes the process of epithelial-mesenchymal transition, which has an essential role in cancer metastasis. Hereby, we review the aberrant expression of Twist in hematopoietic malignancies such as leukemias, lymphomas and myelodysplastic syndrome, which is related with poor prognosis and drug resistance in these disorders. Inactivation of Twist by small RNAs technology or chemotherapeutic inhibitors targeting Twist and upstream or downstream molecules of Twist signaling pathways may be helpful in management of disease to improve treatment strategies in malignancies.

Mesenchymal Stem Cells in Myeloid Malignancies: A Focus on Immune Escaping and Therapeutic Implications

“…Hypomethylating agents are able to demethylate Wnt antagonist gene promoters in vitro [ 147 ], leading to Wnt reexpression and normal myelopoiesis restoration. Similar results were described for the above mentioned gene TWIST, implicated in the pathophysiology of clonal myeloid diseases [ 148 ], whose reexpression in vitro occurred after treatment with hypomethylating agents [ 149 ]. Regarding autophagy, which confers a sort of cell protection in lower risk MDS and becomes defective along with disease progression, it could be another possible target for hypomethylating agents.…”

EMT Factors and Metabolic Pathways in Cancer

“…Expression of TWIST TFs can induce the EMT process and they are upregulated during cancer development (85,86) and progression to metastasis (87). TWIST TFs are also associated with worse patient prognosis (87).…”

MicroRNA Regulation of Epithelial to Mesenchymal Transition

“…They are able to form homo- and heterodimers with each other [ 146 , 147 , 148 , 149 ] and to directly interact with a large set of transcription factors. The Twist factors are overexpressed in most in human cancers and in most cases correlate with high tumor grade, invasiveness, and metastasis [ 150 , 151 , 152 , 153 , 154 , 155 , 156 ].…”