title: Hematopoietic myeloid cell differentiation diminishes nucleotide excision repair.
abstract: Myeloid cell differentiation is the process by which stem cells develop into mature monocytes or granulocytes. This process is achieved by the sequential activation of variety of genes. Disruption of this process can result in immunodeficiency, bone marrow failure syndrome, or leukemia. Acute promyelocytic leukemia (APL) is characterized by the t(15;17) translocation and can be treated by a combination of all-trans retinoic acid (ATRA) and anthracycline. This treatment can induce leukemic cell differentiation, leading to extremely high remission rates. XAB2, a molecule involved in nucleotide excision repair (NER), is downregulated during granulocyte differentiation and shows reduced expression in NB4 APL-derived cells in vitro. Differentiation of APL by ATRA treatment reduced XAB2 expression levels in vivo. These observations suggest that cellular differentiation is associated with reduced NER activity and provides new insights into combined differentiation induction. NB4 cells were more susceptible than the immature myeloid leukemic cell lines, Kasumi-3 and Kasumi-1, to the DNA interstrand crosslinking agent cisplatin.
authors.affiliation: Department of Pediatrics and Developmental Biology, Graduate Medical School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Aoki
authors.forename: Ayako
authors.initials: A
authors.lastname: Sato
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D017930:Genes, Reporter; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000072260:RNA Splicing Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000072260:RNA Splicing Factors; D014157:Transcription Factors; C417244:XAB2 protein, human; D014212:Tretinoin; D008156:Luciferases; D002945:Cisplatin