title: Identification of novel genomic aberrations in AML-M5 in a level of array CGH.
abstract: To assess the possible existence of unbalanced chromosomal abnormalities and delineate the characterization of copy number alterations (CNAs) of acute myeloid leukemia-M5 (AML-M5), R-banding karyotype, oligonucelotide array CGH and FISH were performed in 24 patients with AML-M5. A total of 117 CNAs with size ranging from 0.004 to 146.263 Mb was recognized in 12 of 24 cases, involving all chromosomes other than chromosome 1, 4, X and Y. Cryptic CNAs with size less than 5 Mb accounted for 59.8% of all the CNAs. 12 recurrent chromosomal alterations were mapped. Seven out of them were described in the previous AML studies and five were new candidate AML-M5 associated CNAs, including gains of 3q26.2-qter and 13q31.3 as well as losses of 2q24.2, 8p12 and 14q32. Amplication of 3q26.2-qter was the sole large recurrent chromosomal anomaly and the pathogenic mechanism in AML-M5 was possibly different from the classical recurrent 3q21q26 abnormality in AML. As a tumor suppressor gene, FOXN3, was singled out from the small recurrent CNA of 14q32, however, it is proved that deletion of FOXN3 is a common marker of myeloid leukemia rather than a specific marker for AML-M5 subtype. Moreover, the concurrent amplication of MLL and deletion of CDKN2A were noted and it might be associated with AML-M5. The number of CNA did not show a significant association with clinico-biological parameters and CR number of the 22 patients received chemotherapy. This study provided the evidence that array CGH served as a complementary platform for routine cytogenetic analysis to identify those cryptic alterations in the patients with AML-M5. As a subtype of AML, AML-M5 carries both common recurrent CNAs and unique CNAs, which may harbor novel oncogenes or tumor suppressor genes. Clarifying the role of these genes will contribute to the understanding of leukemogenic network of AML-M5.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P.R. China; Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Pathology, College of Medicine, Korea University, Seoul, South Korea.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Xianfu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Weihong
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Rurong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Shibo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D051858:Forkhead Transcription Factors; D006801:Humans; D007621:Karyotyping; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; C106158:FOXN3 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins
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