ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1‐RUNX1T1 and associated with a better prognosis |
| |
| Authors: | Genki Yamato Norio Shiba Kenichi Yoshida Yuichi Shiraishi Yusuke Hara Kentaro Ohki Jun Okubo Haruna Okuno Kenichi Chiba Hiroko Tanaka Akitoshi Kinoshita Hiroshi Moritake Nobutaka Kiyokawa Daisuke Tomizawa Myoung‐ja Park Manabu Sotomatsu Takashi Taga Souichi Adachi Akio Tawa Keizo Horibe Hirokazu Arakawa Satoru Miyano Seishi Ogawa Yasuhide Hayashi |
| |
| Institution: | 1. Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan;2. Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan;3. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan;4. Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University Kyoto, Japan;5. Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan;6. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan;7. Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan;8. Department of Pediatrics, St. Marianna University School of Medicine Hospital, Kanagawa, Japan;9. Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan;10. Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan;11. Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan;12. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan;13. Department of Pediatrics, National Hospital Organization Osaka National Hospital, Osaka, Japan;14. Director General, Japanese Red Cross Gunma Blood Center, Gunma, Japan |
| |
| Abstract: | ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0–17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1‐RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event‐free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild‐type (5‐year OS, 75% vs. 100% vs. 91% and 5‐year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. |
| |
| Keywords: | |
|
|
