Abstract
Forkhead box (FOX) proteins are a group of transcriptional factors implicated in different cellular functions such as differentiation, proliferation and senescence. A growing number of studies have focused on the relationship between FOX proteins and cancers, particularly hematological neoplasms such as acute myeloid leukemia (AML). FOX proteins are widely involved in AML biology, including leukemogenesis, relapse and drug sensitivity. Here we explore the role of FOX transcription factors in the major AML entities, according to “The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia”, and in the context of the most recurrent gene mutations identified in this heterogeneous disease. Moreover, we report the new evidences about the role of FOX proteins in drug sensitivity, mechanisms of chemoresistance, and possible targeting for personalized therapies.
Highlights
Forkhead box (FOX) proteins are an extended group of transcriptional factors characterized by the presence of an evolutionary conserved DNA-binding domain (DBD) named “winged-helix”or “fork-head”
The mechanisms of gene expression regulation controlled by FOX proteins are, in some cases, The ability of FOX proteins to contribute to the control of several fundamental signaling pathways so intricate that some FOX proteins are themselves the target of other members of the same gene and of all the aspects of development and cell fate allows this superfamily of transcription factors to be family, as shown by Karadedou et al that described the mechanisms by which FOXO3A and FOXM1 heavily implicated in cancer initiation and FOX factors have beentarget showngenes to play antagonize the activity of one another by progression
FOXO genes (FOXO1, FOXO3, FOXO4 and FOXO6) are frequently reported as tumour suppressors in several cancers [27,28,29,30,31,32,33,34,35], Lin et al recently highlighted a new role of FOXO1 as an oncogene, clearly showing that the role of Forkhead box proteins depends on cellular context [19]
Summary
Forkhead box (FOX) proteins are an extended group of transcriptional factors characterized by the presence of an evolutionary conserved DNA-binding domain (DBD) named “winged-helix”. The fine regulation of gene expression performed by FOX proteins is due to the tissue and/or networks, the main of which are: development, differentiation, maintenance of multipotency, cell-specific expression, but is due to the post-translational modifications that mainly include proliferation, metabolism, repair, celland cycle progression,[16,17]. The mechanisms of gene expression regulation controlled by FOX proteins are, in some cases, The ability of FOX proteins to contribute to the control of several fundamental signaling pathways so intricate that some FOX proteins are themselves the target of other members of the same gene and of all the aspects of development and cell fate allows this superfamily of transcription factors to be family, as shown by Karadedou et al that described the mechanisms by which FOXO3A and FOXM1 heavily implicated in cancer initiation and FOX factors have beentarget showngenes to play antagonize the activity of one another by progression. We try to highlight the crucial role that FOX transcription factors play in acute myeloid leukemia development and progression, their role as potential direct and/or indirect therapeutic targets and as biomarkers of drug response and/or resistance
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