title: Clinical characteristics and prognosis of acute myeloid leukemia associated with DNA-methylation regulatory gene mutations.
abstract: In recent years, it has been reported that the frequency of DNA-methylation regulatory gene mutations - mutations of the genes that regulate gene expression through DNA methylation - is high in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. We studied 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutations were observed in 135 of the 308 cases (43.8%). Acute myeloid leukemia associated with a DNA-methylation regulatory gene mutation was more frequent in older patients (P<0.0001) and in patients with intermediate cytogenetic risk (P<0.0001) accompanied by a high white blood cell count (P=0.0032). DNA-methylation regulatory gene mutation was an unfavorable prognostic factor for overall survival in the whole cohort (P=0.0018), in patients aged ≤70 years, in patients with intermediate cytogenetic risk, and in FLT3-ITD-negative patients (P=0.0409). Among the patients with DNA-methylation regulatory gene mutations, 26.7% were found to have two or more such mutations and prognosis worsened with increasing number of mutations. In multivariate analysis DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival (P=0.0424). However, patients with a DNA-methylation regulatory gene mutation who underwent allogeneic stem cell transplantation in first remission had a significantly better prognosis than those who did not undergo such transplantation (P=0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ryotokuji
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan y-hiroki@fd6.so-net.ne.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Hematology, Nagano Red Cross Hospital, Tokyo, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Ueki
authors.affiliation: Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Usuki
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Saiko
authors.initials: S
authors.lastname: Kurosawa
authors.affiliation: Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kawata
authors.affiliation: Department of Hematology, Yokohama Minami Kyousai Hospital, Kanagawa, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tajika
authors.affiliation: Department of Hematology, Yokohama Minami Kyousai Hospital, Kanagawa, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Gomi
authors.affiliation: Division of Hematology, Saitama Medical Center Jichi Medical University, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Omori
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Marumo
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yui
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Terada
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Fukunaga
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Hirakawa
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Kunihito
authors.initials: K
authors.lastname: Arai
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kitano
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kosaka
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Tamai
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakita
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002871:Chromosome Banding; D003131:Combined Modality Therapy; D019175:DNA Methylation; D005260:Female; D020440:Gene Duplication; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis; D020080:Tandem Repeat Sequences; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D051941:fms-Like Tyrosine Kinase 3