KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): A study of the Japanese ChildhoodAMLCooperative Study Group

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

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Abstract

Patients with t(8;21) acute myeloid leukemia (AML) are considered to have a good prognosis; however, approximately 50% of them relapse. The genetic alterations associated with a poor outcome in t(8;21) AML remain unknown. Recently, aberrations of receptor tyrosine kinases (RTKs) were frequently found in patients with AML. However, the prevalence and prognostic impact of RTK aberrations in pediatric t(8;21) AML remains undetermined. Here, we found the kinase domain mutations of the KIT gene in 8 (17.4%) of 46 patients with t(8;21) AML among newly diagnosed pediatric patients with AML treated on the AML99 protocol in Japan. Significant differences between patients with or without KIT mutations were observed in the 4-year overall survival (50.0% versus 97.4%, P = .001), disease-free survival (37.5% versus 94.7%, P <.001) and relapse rate (47.0% versus 2.7%, P <.001). Furthermore, FLT3 internal tandem duplication was found in only 2 (4.3%) patients. These results suggested that KIT mutations are strongly associated with a poor prognosis in pediatric t(8;21) AML.

Original languageEnglish
Pages (from-to)1806-1809
Number of pages4
JournalBlood
Volume107
Issue number5
DOIs
Publication statusPublished - Mar 1 2006
Externally publishedYes

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Pediatrics
Acute Myeloid Leukemia
Receptor Protein-Tyrosine Kinases
Aberrations
Mutation
Phosphotransferases
Genes
Recurrence
Disease-Free Survival
Japan
Survival

ASJC Scopus subject areas

  • Hematology

Cite this

KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21) : A study of the Japanese ChildhoodAMLCooperative Study Group. / Shimada, Akira; Taki, Tomohiko; Tabuchi, Ken; Tawa, Akio; Horibe, Keizo; Tsuchida, Masahiro; Hanada, Ryoji; Tsukimoto, Ichiro; Hayashi, Yasuhide.

In: Blood, Vol. 107, No. 5, 01.03.2006, p. 1806-1809.

Research output: Contribution to journalArticle

Shimada, Akira ; Taki, Tomohiko ; Tabuchi, Ken ; Tawa, Akio ; Horibe, Keizo ; Tsuchida, Masahiro ; Hanada, Ryoji ; Tsukimoto, Ichiro ; Hayashi, Yasuhide. / KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21) : A study of the Japanese ChildhoodAMLCooperative Study Group. In: Blood. 2006 ; Vol. 107, No. 5. pp. 1806-1809.
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abstract = "Patients with t(8;21) acute myeloid leukemia (AML) are considered to have a good prognosis; however, approximately 50{\%} of them relapse. The genetic alterations associated with a poor outcome in t(8;21) AML remain unknown. Recently, aberrations of receptor tyrosine kinases (RTKs) were frequently found in patients with AML. However, the prevalence and prognostic impact of RTK aberrations in pediatric t(8;21) AML remains undetermined. Here, we found the kinase domain mutations of the KIT gene in 8 (17.4{\%}) of 46 patients with t(8;21) AML among newly diagnosed pediatric patients with AML treated on the AML99 protocol in Japan. Significant differences between patients with or without KIT mutations were observed in the 4-year overall survival (50.0{\%} versus 97.4{\%}, P = .001), disease-free survival (37.5{\%} versus 94.7{\%}, P <.001) and relapse rate (47.0{\%} versus 2.7{\%}, P <.001). Furthermore, FLT3 internal tandem duplication was found in only 2 (4.3{\%}) patients. These results suggested that KIT mutations are strongly associated with a poor prognosis in pediatric t(8;21) AML.",
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