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 disease-free 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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Acknowledgments
Committee members of the Japanese Childhood AML Cooperative Study Group who contributed data to this study include Akira Morimoto, Department of Pediatrics, Kyoto Prefectural University of Medicine; Hiromasa Yabe, Department of Pediatrics, Tokai University School of Medicine; Kazuko Hamamoto, Department of Pediatrics, Hiroshima Red Cross Hospital; Shigeru Tsuchiya, Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University; Yuichi Akiyama, Department of Pediatrics, National Hospital Organization Kyoto Medical Center; Hisato Kigasawa, Department of Hematology, Kanagawa Children’s Medical Center; Akira Ohara, First Department of Pediatrics, Toho University School of Medicine; Hideki Nakayama, Department of Pediatrics, Hamanomachi Hospital; Kazuko Kudo, Department of Pediatrics, Nagoya University Graduate School of Medicine; and Masue Imaizumi, Department of Hematology/Oncology, Miyagi Prefectural Children’s Hospital. This work was supported by a grant for Cancer Research and a grant for Research on Children and Families from the Ministry of Health, Labour, and Welfare of Japan, a Grant-in-Aid for Scientific Research (B, C) and Exploratory Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a Research grant for Gunma Prefectural Hospitals.
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Sano, H., Shimada, A., Taki, T. et al. 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. Int J Hematol 95, 509–515 (2012). https://doi.org/10.1007/s12185-012-1033-x
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DOI: https://doi.org/10.1007/s12185-012-1033-x