title: Targeting forkhead box transcription factors FOXM1 and FOXO in leukemia (Review).
abstract: Deregulation of forkhead box (FOX) proteins has been found in many genetic diseases and malignancies including leukemia. Leukemia is a common neoplastic disease of the blood or bone marrow characterized by the presence of immature leukocytes and is one of the leading causes of death due to cancer. Forkhead transcription factors, FOXM1 and FOXO family members (FOXOs), are important mediators in leukemia development. Aberrant expression of FOXM1 and FOXOs results in leukemogenesis. Usually the expression of FOXM1 is upregulated, whereas the expression of FOXOs is downregulated due to phosphorylation, nuclear exclusion and degradation in leukemia. On the one hand, FOXOs are bona fide tumor suppressors, on the other hand, active FOXOs maintain leukemia stem cells and stimulate drug resistance genes, contributing to leukemogenesis. FOXM1 and FOXOs have been proven to be potential targets for the development of leukemia therapeutics. They are also valuable diagnostic and prognostic markers in leukemia for clinical applications. This review summarizes the present knowledge concerning the molecular mechanisms by which FOXM1 and FOXOs modulate leukemogenesis and leukemia development, the clinical relevance of these FOX proteins in leukemia and related areas that warrant further investigation.
authors.affiliation: Department of Biomedical Engineering, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D000072278:Forkhead Box Protein M1; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C107585:FOXM1 protein, human; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; C108803:FOXO4 protein, human; C478770:FOXO6 protein, human; D000072278:Forkhead Box Protein M1; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D014157:Transcription Factors