Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia: A study of the Japanese childhood AML cooperative study group

Akira Shimada, Tomohiko Taki, Ken Tabuchi, Takeshi Taketani, Ryoji Hanada, Akio Tawa, Masahiro Tsuchida, Keizo Horibe, Ichiro Tsukimoto, Yasuhide Hayashi

Research output: Contribution to journalArticle

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Abstract

Background. Mixed-lineage leukemia (MLL)-partial tandem duplication (PTD) is associated with poor prognosis in adult acute myeloid leukemia (AML), but its relationship to pediatric AML is unknown. Procedure. One hundred fifty-eight newly diagnosed AML patients, including 13 FAB-M3 and 10 Down syndrome (DS) patients, who were treated on the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed for MLL-PTD, as well as internal tandem duplication (ITD) and the kinase domain mutation (D835Mt) in the FLT3 gene. Results. We found MLL-PTD in 21 (13.3%) of 158 AML patients, but not in FAB-M3 or DS patients. The differences between patients with and without MLL-PTD were significant for 3-year overall survival (OS) (56.3% vs. 83.2%, P=0.018), disease-free survival (DFS) (41.7% vs. 69.6%, P=0.010), and relapse rate (RR) (54.3% vs. 27.6%, P=0.00851 of 135 AML patients excluding the FAB-M3 and DS patients. Furthermore, ITD and D835Mt in the FLT3 gene were found in 17 (12.6%) and 8 (5.9%) of these 135 patients, respectively. The differences between patients with FLT3-ITD and the wild-type allele were significant for 3-year OS (35.3% and 84.3%, P <0.0000001), DFS (40.0% and 66.9%, P <0.003), and RR (52.4% and 30.3%, P <0.005). Coduplication of both genes was found in only 3 (1.9%) patients. Conclusion. AML patients with FLT3-ITD, but not D835Mt, showed a poor prognosis. AML patients with MLL-PTD were also correlated with poor prognosis in this study.

Original languageEnglish
Pages (from-to)264-269
Number of pages6
JournalPediatric Blood and Cancer
Volume50
Issue number2
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

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Acute Myeloid Leukemia
Leukemia
Pediatrics
Down Syndrome
Disease-Free Survival
Genes
Recurrence
Survival
Clinical Protocols
Phosphotransferases
Alleles
Mutation

Keywords

  • AML
  • Childhood
  • Cytogenetics
  • FLT3
  • MLL
  • Tandem duplication

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia : A study of the Japanese childhood AML cooperative study group. / Shimada, Akira; Taki, Tomohiko; Tabuchi, Ken; Taketani, Takeshi; Hanada, Ryoji; Tawa, Akio; Tsuchida, Masahiro; Horibe, Keizo; Tsukimoto, Ichiro; Hayashi, Yasuhide.

In: Pediatric Blood and Cancer, Vol. 50, No. 2, 02.2008, p. 264-269.

Research output: Contribution to journalArticle

Shimada, Akira ; Taki, Tomohiko ; Tabuchi, Ken ; Taketani, Takeshi ; Hanada, Ryoji ; Tawa, Akio ; Tsuchida, Masahiro ; Horibe, Keizo ; Tsukimoto, Ichiro ; Hayashi, Yasuhide. / Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia : A study of the Japanese childhood AML cooperative study group. In: Pediatric Blood and Cancer. 2008 ; Vol. 50, No. 2. pp. 264-269.
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title = "Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia: A study of the Japanese childhood AML cooperative study group",
abstract = "Background. Mixed-lineage leukemia (MLL)-partial tandem duplication (PTD) is associated with poor prognosis in adult acute myeloid leukemia (AML), but its relationship to pediatric AML is unknown. Procedure. One hundred fifty-eight newly diagnosed AML patients, including 13 FAB-M3 and 10 Down syndrome (DS) patients, who were treated on the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed for MLL-PTD, as well as internal tandem duplication (ITD) and the kinase domain mutation (D835Mt) in the FLT3 gene. Results. We found MLL-PTD in 21 (13.3{\%}) of 158 AML patients, but not in FAB-M3 or DS patients. The differences between patients with and without MLL-PTD were significant for 3-year overall survival (OS) (56.3{\%} vs. 83.2{\%}, P=0.018), disease-free survival (DFS) (41.7{\%} vs. 69.6{\%}, P=0.010), and relapse rate (RR) (54.3{\%} vs. 27.6{\%}, P=0.00851 of 135 AML patients excluding the FAB-M3 and DS patients. Furthermore, ITD and D835Mt in the FLT3 gene were found in 17 (12.6{\%}) and 8 (5.9{\%}) of these 135 patients, respectively. The differences between patients with FLT3-ITD and the wild-type allele were significant for 3-year OS (35.3{\%} and 84.3{\%}, P <0.0000001), DFS (40.0{\%} and 66.9{\%}, P <0.003), and RR (52.4{\%} and 30.3{\%}, P <0.005). Coduplication of both genes was found in only 3 (1.9{\%}) patients. Conclusion. AML patients with FLT3-ITD, but not D835Mt, showed a poor prognosis. AML patients with MLL-PTD were also correlated with poor prognosis in this study.",
keywords = "AML, Childhood, Cytogenetics, FLT3, MLL, Tandem duplication",
author = "Akira Shimada and Tomohiko Taki and Ken Tabuchi and Takeshi Taketani and Ryoji Hanada and Akio Tawa and Masahiro Tsuchida and Keizo Horibe and Ichiro Tsukimoto and Yasuhide Hayashi",
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TY - JOUR

T1 - Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia

T2 - A study of the Japanese childhood AML cooperative study group

AU - Shimada, Akira

AU - Taki, Tomohiko

AU - Tabuchi, Ken

AU - Taketani, Takeshi

AU - Hanada, Ryoji

AU - Tawa, Akio

AU - Tsuchida, Masahiro

AU - Horibe, Keizo

AU - Tsukimoto, Ichiro

AU - Hayashi, Yasuhide

PY - 2008/2

Y1 - 2008/2

N2 - Background. Mixed-lineage leukemia (MLL)-partial tandem duplication (PTD) is associated with poor prognosis in adult acute myeloid leukemia (AML), but its relationship to pediatric AML is unknown. Procedure. One hundred fifty-eight newly diagnosed AML patients, including 13 FAB-M3 and 10 Down syndrome (DS) patients, who were treated on the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed for MLL-PTD, as well as internal tandem duplication (ITD) and the kinase domain mutation (D835Mt) in the FLT3 gene. Results. We found MLL-PTD in 21 (13.3%) of 158 AML patients, but not in FAB-M3 or DS patients. The differences between patients with and without MLL-PTD were significant for 3-year overall survival (OS) (56.3% vs. 83.2%, P=0.018), disease-free survival (DFS) (41.7% vs. 69.6%, P=0.010), and relapse rate (RR) (54.3% vs. 27.6%, P=0.00851 of 135 AML patients excluding the FAB-M3 and DS patients. Furthermore, ITD and D835Mt in the FLT3 gene were found in 17 (12.6%) and 8 (5.9%) of these 135 patients, respectively. The differences between patients with FLT3-ITD and the wild-type allele were significant for 3-year OS (35.3% and 84.3%, P <0.0000001), DFS (40.0% and 66.9%, P <0.003), and RR (52.4% and 30.3%, P <0.005). Coduplication of both genes was found in only 3 (1.9%) patients. Conclusion. AML patients with FLT3-ITD, but not D835Mt, showed a poor prognosis. AML patients with MLL-PTD were also correlated with poor prognosis in this study.

AB - Background. Mixed-lineage leukemia (MLL)-partial tandem duplication (PTD) is associated with poor prognosis in adult acute myeloid leukemia (AML), but its relationship to pediatric AML is unknown. Procedure. One hundred fifty-eight newly diagnosed AML patients, including 13 FAB-M3 and 10 Down syndrome (DS) patients, who were treated on the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed for MLL-PTD, as well as internal tandem duplication (ITD) and the kinase domain mutation (D835Mt) in the FLT3 gene. Results. We found MLL-PTD in 21 (13.3%) of 158 AML patients, but not in FAB-M3 or DS patients. The differences between patients with and without MLL-PTD were significant for 3-year overall survival (OS) (56.3% vs. 83.2%, P=0.018), disease-free survival (DFS) (41.7% vs. 69.6%, P=0.010), and relapse rate (RR) (54.3% vs. 27.6%, P=0.00851 of 135 AML patients excluding the FAB-M3 and DS patients. Furthermore, ITD and D835Mt in the FLT3 gene were found in 17 (12.6%) and 8 (5.9%) of these 135 patients, respectively. The differences between patients with FLT3-ITD and the wild-type allele were significant for 3-year OS (35.3% and 84.3%, P <0.0000001), DFS (40.0% and 66.9%, P <0.003), and RR (52.4% and 30.3%, P <0.005). Coduplication of both genes was found in only 3 (1.9%) patients. Conclusion. AML patients with FLT3-ITD, but not D835Mt, showed a poor prognosis. AML patients with MLL-PTD were also correlated with poor prognosis in this study.

KW - AML

KW - Childhood

KW - Cytogenetics

KW - FLT3

KW - MLL

KW - Tandem duplication

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DO - 10.1002/pbc.21318

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