RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse

A study of the japanese childhood AML cooperative study group

Hirozumi Sano, Akira Shimada, Tomohiko Taki, Chisato Murata, Myoung Ja Park, Manabu Sotomatsu, Ken Tabuchi, Akio Tawa, Ryoji Kobayashi, Keizo Horibe, Masahiro Tsuchida, Ryoji Hanada, Ichiro Tsukimoto, Yasuhide Hayashi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Mutations in RAS are frequent in acute myeloid leukemia (AML), and are thought to contribute to leukemogenesis in a subset of patients; however, their prognostic significance has not been firmly established. One hundred and fifty-seven pediatric patients with AML were analyzed for NRAS and KRAS mutations around hot spots at codons 12, 13, and 61. Twenty-nine patients (18.5%) had an activating mutation of RAS. We found KRAS mutations to be more frequent than NRAS mutations (18/29, 62.1% of patients with RAS mutation), in contrast to previous reports (18-40%). The frequency of RAS mutation was higher in French-American-British types M4 and M5 than other types (P = 0.02). There were no significant differences in other clinical manifestations or distribution in cytogenetic subgroups, or aberrations of other genes, including KIT mutation, FLT3-ITD, and MLL-PTD, between patients with and without RAS mutations. No significant differences were observed in the 3-year overall survival and diseasefree survival; however, the presence of RAS mutation was related to late relapse. The occurrence of clinical events at relatively late period should be monitored for in AML patients with mutations in RAS.

Original languageEnglish
Pages (from-to)509-515
Number of pages7
JournalInternational Journal of Hematology
Volume95
Issue number5
DOIs
Publication statusPublished - May 2012
Externally publishedYes

Fingerprint

Leukemia, Myelomonocytic, Acute
Leukemia, Monocytic, Acute
Acute Myeloid Leukemia
Recurrence
Mutation
Survival
Mutation Rate
Codon
Cytogenetics

Keywords

  • Acute myeloid leukemia
  • FAB
  • Late relapse
  • Prognosis
  • RAS

ASJC Scopus subject areas

  • Hematology

Cite this

RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse : A study of the japanese childhood AML cooperative study group. / Sano, Hirozumi; Shimada, Akira; Taki, Tomohiko; Murata, Chisato; Park, Myoung Ja; Sotomatsu, Manabu; Tabuchi, Ken; Tawa, Akio; Kobayashi, Ryoji; Horibe, Keizo; Tsuchida, Masahiro; Hanada, Ryoji; Tsukimoto, Ichiro; Hayashi, Yasuhide.

In: International Journal of Hematology, Vol. 95, No. 5, 05.2012, p. 509-515.

Research output: Contribution to journalArticle

Sano, H, Shimada, A, Taki, T, Murata, C, Park, MJ, Sotomatsu, M, Tabuchi, K, Tawa, A, Kobayashi, R, Horibe, K, Tsuchida, M, Hanada, R, Tsukimoto, I & Hayashi, Y 2012, 'RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse: A study of the japanese childhood AML cooperative study group', International Journal of Hematology, vol. 95, no. 5, pp. 509-515. https://doi.org/10.1007/s12185-012-1033-x
Sano, Hirozumi ; Shimada, Akira ; Taki, Tomohiko ; Murata, Chisato ; Park, Myoung Ja ; Sotomatsu, Manabu ; Tabuchi, Ken ; Tawa, Akio ; Kobayashi, Ryoji ; Horibe, Keizo ; Tsuchida, Masahiro ; Hanada, Ryoji ; Tsukimoto, Ichiro ; Hayashi, Yasuhide. / RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse : A study of the japanese childhood AML cooperative study group. In: International Journal of Hematology. 2012 ; Vol. 95, No. 5. pp. 509-515.
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abstract = "Mutations in RAS are frequent in acute myeloid leukemia (AML), and are thought to contribute to leukemogenesis in a subset of patients; however, their prognostic significance has not been firmly established. One hundred and fifty-seven pediatric patients with AML were analyzed for NRAS and KRAS mutations around hot spots at codons 12, 13, and 61. Twenty-nine patients (18.5{\%}) had an activating mutation of RAS. We found KRAS mutations to be more frequent than NRAS mutations (18/29, 62.1{\%} of patients with RAS mutation), in contrast to previous reports (18-40{\%}). The frequency of RAS mutation was higher in French-American-British types M4 and M5 than other types (P = 0.02). There were no significant differences in other clinical manifestations or distribution in cytogenetic subgroups, or aberrations of other genes, including KIT mutation, FLT3-ITD, and MLL-PTD, between patients with and without RAS mutations. No significant differences were observed in the 3-year overall survival and diseasefree survival; however, the presence of RAS mutation was related to late relapse. The occurrence of clinical events at relatively late period should be monitored for in AML patients with mutations in RAS.",
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AU - Sano, Hirozumi

AU - Shimada, Akira

AU - Taki, Tomohiko

AU - Murata, Chisato

AU - Park, Myoung Ja

AU - Sotomatsu, Manabu

AU - Tabuchi, Ken

AU - Tawa, Akio

AU - Kobayashi, Ryoji

AU - Horibe, Keizo

AU - Tsuchida, Masahiro

AU - Hanada, Ryoji

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AU - Hayashi, Yasuhide

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AB - Mutations in RAS are frequent in acute myeloid leukemia (AML), and are thought to contribute to leukemogenesis in a subset of patients; however, their prognostic significance has not been firmly established. One hundred and fifty-seven pediatric patients with AML were analyzed for NRAS and KRAS mutations around hot spots at codons 12, 13, and 61. Twenty-nine patients (18.5%) had an activating mutation of RAS. We found KRAS mutations to be more frequent than NRAS mutations (18/29, 62.1% of patients with RAS mutation), in contrast to previous reports (18-40%). The frequency of RAS mutation was higher in French-American-British types M4 and M5 than other types (P = 0.02). There were no significant differences in other clinical manifestations or distribution in cytogenetic subgroups, or aberrations of other genes, including KIT mutation, FLT3-ITD, and MLL-PTD, between patients with and without RAS mutations. No significant differences were observed in the 3-year overall survival and diseasefree survival; however, the presence of RAS mutation was related to late relapse. The occurrence of clinical events at relatively late period should be monitored for in AML patients with mutations in RAS.

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