title: Age-associated difference in gene expression of paediatric acute myelomonocytic lineage leukaemia (FAB M4 and M5 subtypes) and its correlation with prognosis.
abstract: Acute myeloid leukaemia, French-American-British M4 and M5 subtypes (AML-M4/M5) is frequently associated with MLL gene rearrangement and its incidence is relatively high among infants. Clinically, paediatric AML-M4/M5 has been considered as an intermediate or undefined prognostic group. In this study, we analysed gene expression of 40 paediatric AML-M4/M5 patients excluding inv(16) and t(8;21) patients, and found striking differences among the patients in an age-associated manner. In particular, most of the infants displayed very distinct gene expression. On the basis of this difference, we divided paediatric patients into three subgroups (A, B and C) with the average age of 0.3, 3.1 and 6.6 years old respectively. All subgroups included patients with MLL gene rearrangement as well as normal and other karyotypes. Surprisingly, gene expression signatures of MLL gene rearrangement differed substantially among these subgroups. In addition, subgroup C presented extremely poor outcome (3-year event-free survival 28%) whilst eight patients with MLL gene rearrangement in subgroup C had all relapsed within 18 months. These results suggest that age is an important factor contributing to the biology of AML-M4/M5 and the sub-grouping procedures developed in this study could be a powerful tool to identify unfavourable risk patients within paediatric AML-M4/M5.
authors.affiliation: Genetics Division, National Cancer Centre Research Institute, Tokyo, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Jo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsukimoto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Norio
authors.initials: N
authors.lastname: Asou
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Mitani
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
mesh_terms: D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051788:Myeloid-Lymphoid Leukemia Protein