Age-associated difference in gene expression of paediatric acute myelomonocytic lineage leukaemia (FAB M4 and M5 subtypes) and its correlation with prognosis

Aoi Jo, Ichiro Tsukimoto, Eiichi Ishii, Norio Asou, Sachiyo Mitani, Akira Shimada, Takashi Igarashi, Yasuhide Hayashi, Hitoshi Ichikawa

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)917-929
Number of pages13
JournalBritish Journal of Haematology
Volume144
Issue number6
DOIs
Publication statusPublished - Mar 2009

Keywords

  • Acute myeloid leukaemia
  • Gene expression profiling
  • MLL
  • Microarray
  • Prognostic factors

ASJC Scopus subject areas

  • Hematology

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