@article{0e33ffdf6cfd4e0582223cbe358d4b30,
title = "High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: The results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial",
abstract = "Recent reports described the NUP98-NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98-NSD1 fusion. PRDM16 gene expression levels were measured via real-time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio ≥0·010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P < 0·001; inv(16), 0% vs. 100%, P < 0·001; KMT2A (also termed MLL)- partial tandem duplication, 100% vs. 0%, P < 0·001; NUP98-NSD1, 100% vs. 0%, P < 0·001. The overall survival (OS) and event-free survival (EFS) among PRDM16-overexpressing patients were significantly worse than in patients with low PRDM16 expression (3-year OS: 51% vs. 81%, P < 0·001, 3-year EFS: 32% vs. 64%, P < 0·001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3-internal tandem duplication-positive AML patients (3-year OS: high = 30% vs. low = 70%, P < 0·001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate-risk cytogenetic profiles and was independently associated with an adverse outcome.",
keywords = "AML, FLT3-ITD, Gene expression, KMT2A-PTD, NUP98-NSD1, PRDM16",
author = "Norio Shiba and Kentaro Ohki and Tohru Kobayashi and Yusuke Hara and Genki Yamato and Reo Tanoshima and Hitoshi Ichikawa and Daisuke Tomizawa and Park, {Myoung Ja} and Akira Shimada and Manabu Sotomatsu and Hirokazu Arakawa and Keizo Horibe and Souichi Adachi and Takashi Taga and Akio Tawa and Yasuhide Hayashi",
note = "Funding Information: The authors thank Dr. Eisuke Inoue for his valuable assistance with statistical analysis. This study was performed as a research programme of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan and was supported by a Cancer Research Grant, Grant for Research on Children and Families, and Research on Intractable Diseases, Health, and Labour Sciences Research Grants from the Ministry of Health, Labour, and Welfare of Japan; a Grant-in-Aid for Scientific Research (B_24390268, C_25461611, 26461598, and 26461599) and Exploratory Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NiBio) of Japan; the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED_15ck0106066h0002); and the Kawano Memorial Public Interest Incorporated Foundation for Promotion of Paediatrics. The authors would like to thank Enago (www. enago.jp) for the English language review.\ Publisher Copyright: {\textcopyright} 2016 John Wiley & Sons Ltd.",
year = "2016",
month = feb,
day = "1",
doi = "10.1111/bjh.13869",
language = "English",
volume = "172",
pages = "581--591",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "4",
}