title: Late appearance of a Philadelphia chromosome in a patient with therapy-related acute myeloid leukemia and high expression of EVI1.
abstract: A 17-year-old boy developed therapy-related acute myeloid leukemia (t-AML) 3 years after the cessation of chemo- and radiotherapy for undifferentiated sarcoma of the liver. At the onset of the t-AML, his white blood cell count was 900/microL with a 46,XY,t(2;3)(p21;q26),del(5)(q?) karyotype. Despite intensive chemotherapy and two hematopoietic stem cell transplants, he died of the leukemia. At the terminal phase, his white blood cell count surpassed 30,000/microL and the Philadelphia (Ph) chromosome appeared. Expression of EVI1 in bone marrow cells was remarkably high at the onset of t-AML, although it was not detected at the end of therapy for the sarcoma. Polymerase chain reaction analysis of bone marrow cells revealed that mRNA for the bcr-abl chimera was negative at the onset of t-AML and positive at the terminal phase. These results suggest that EVI1 overexpression was the major factor contributing to leukemogenesis, and the late appearance of the Ph chromosome is closely associated with the progression to an aggressive form of leukemia.
authors.affiliation: Department of Pediatrics, Kyoto City Hospital, 1-2 Mibuhigushitakada-cho, Nakagyo-ku, Kyoto, Japan. shigeky@koto.kpu-m.ac.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yagyu
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Kakazu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujiki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakase
authors.forename: Tomoko
authors.initials: T
authors.lastname: Iehara
authors.forename: Hajime
authors.initials: H
authors.lastname: Hosoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuroda
mesh_terms: D000293:Adolescent; D004268:DNA-Binding Proteins / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics; D008113:Liver Neoplasms / Q000628:therapy; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D016609:Neoplasms, Second Primary / Q000235:genetics*; D010677:Philadelphia Chromosome; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012509:Sarcoma / Q000628:therapy; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D016044:Fusion Proteins, bcr-abl