title: The effect of amifostine on differentiation of the human megakaryoblastic Dami cell line.
abstract: Amifostine is a cytoprotective drug that was initially used to control and treat nuclear radiation injury and is currently used to provide organ protection in cancer patients receiving chemotherapy. Clinical studies have also found that amifostine has some efficacy in the treatment of cytopenia caused by conditions such as myelodysplastic syndrome and immune thrombocytopenia, both of which involve megakaryocyte maturation defects. We hypothesized that amifostine induced the differentiation of megakaryocytes and investigated this by exposing the human Dami megakaryocyte leukemia cell line to amifostine (1 mmol/L). After 12 days of amifostine exposure, optical microscopy showed that the proportion of Dami cells with diameters >20 μm had increased to 24.63%. Transmission electron microscopy identified the development of a platelet demarcation membrane system, while flow cytometry detected increased CD41a expression and decreased CD33 expression on the Dami cell surface. Ploidy analysis found that the number of polyploid cells with >4N DNA content increased to 27.96%. We did not detect any elevation in the mRNA or protein levels of megakaryocytic differentiation-associated transcription factors GATA-binding factor 1 (GATA-1) and nuclear factor, erythroid 2 (NF-E2), but nuclear import assay revealed an increased nuclear translocation of these proteins. These findings indicate that amifostine induced the differentiation of Dami cells into mature megakaryocytes via a mechanism involving increased nuclear translocation of the transcription factors, NF-E2 and GATA-1.
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, 100853, China.|Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.|Department of Hematology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.|Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Chinese PLA Rocket General Hospital, Beijing, 100800, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Chi
authors.affiliation: Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.
authors.forename: Long-Long
authors.initials: LL
authors.lastname: Luo
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Hong-Qi
authors.initials: HQ
authors.lastname: Yang
authors.affiliation: Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Lang
authors.affiliation: Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Geng
authors.affiliation: Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Qiao
authors.affiliation: Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, 100048, China.
authors.forename: Xiao-Xiong
authors.initials: XX
authors.lastname: Wu
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Zhu
authors.affiliation: Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, 100039, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Xue-Chun
authors.initials: XC
authors.lastname: Lu
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection; D006801:Humans; D016130:Immunophenotyping; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology* / Q000187:drug effects*; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011123:Polyploidy; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; D004999:Amifostine
keywords: Amifostine; CD41a; DNA ploidy; Dami cells; transcription factor