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 MD
Department of Hematology/Oncology, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan
Search for more papers by this authorTomohiko Taki MD
Department of Molecular Laboratory Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan
Search for more papers by this authorKen Tabuchi MD
Department of Hematology, Kanagawa Children's Medical Center, Mutsukawa 2-138-4, Minami-ku, Yokohama, Kanagawa, Japan
Search for more papers by this authorTakeshi Taketani MD
Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan
Search for more papers by this authorRyoji Hanada MD
Division of Hematology/Oncology, Saitama Children's Medical Center, 2100, Magome, Saitama, Saitama, Japan
Search for more papers by this authorAkio Tawa MD
Department of Pediatrics, National Hospital Organization, Osaka National Hospital, 2-1-14, Hoenzaka, Chuoku, Osaka, Japan
Search for more papers by this authorMasahiro Tsuchida MD
Department of Pediatrics, Ibaraki Children's Hospital, 3-3-1, Futabadai, Mito, Ibaraki, Japan
Search for more papers by this authorKeizo Horibe MD
Clinical Research Center, National Hospital Organization, Nagoya Medical Center, 4-1-1, Sannomaru, Nakaku, Nagoya, Aichi, Japan
Search for more papers by this authorIchiro Tsukimoto MD
First Department of Pediatrics, Toho University School of Medicine, 6-11-1, Omori-nishi, Otaku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Yasuhide Hayashi MD
Department of Hematology/Oncology, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan
Director, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan.===Search for more papers by this authorAkira Shimada MD
Department of Hematology/Oncology, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan
Search for more papers by this authorTomohiko Taki MD
Department of Molecular Laboratory Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan
Search for more papers by this authorKen Tabuchi MD
Department of Hematology, Kanagawa Children's Medical Center, Mutsukawa 2-138-4, Minami-ku, Yokohama, Kanagawa, Japan
Search for more papers by this authorTakeshi Taketani MD
Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan
Search for more papers by this authorRyoji Hanada MD
Division of Hematology/Oncology, Saitama Children's Medical Center, 2100, Magome, Saitama, Saitama, Japan
Search for more papers by this authorAkio Tawa MD
Department of Pediatrics, National Hospital Organization, Osaka National Hospital, 2-1-14, Hoenzaka, Chuoku, Osaka, Japan
Search for more papers by this authorMasahiro Tsuchida MD
Department of Pediatrics, Ibaraki Children's Hospital, 3-3-1, Futabadai, Mito, Ibaraki, Japan
Search for more papers by this authorKeizo Horibe MD
Clinical Research Center, National Hospital Organization, Nagoya Medical Center, 4-1-1, Sannomaru, Nakaku, Nagoya, Aichi, Japan
Search for more papers by this authorIchiro Tsukimoto MD
First Department of Pediatrics, Toho University School of Medicine, 6-11-1, Omori-nishi, Otaku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Yasuhide Hayashi MD
Department of Hematology/Oncology, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan
Director, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma 377-8577, Japan.===Search for more papers by this authorAbstract
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 = 0.0085) 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. Pediatr Blood Cancer 2008;50:264–269. © 2007 Wiley-Liss, Inc.
Supporting Information
This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1545-5009/suppmat .
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| jws-pbc.21318.fig1.doc38.5 KB | Supporting Information file jws-pbc.21318.fig1.doc |
| jws-pbc.21318.fig2.tif76.4 KB | Supporting Information file jws-pbc.21318.fig2.tif |
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