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Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse by Manoj Garg, Yasunobu Nagata, Deepika Kanojia, Anand Mayakonda, Kenichi Yoshida, Sreya Haridas Keloth, Zhi Jiang Zang, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Ling-Wen Ding, Tamara Alpermann, Qiao-Yang Sun, De-Chen Lin, Wenwen Chien, Vikas Madan, Li-Zhen Liu, Kar-Tong Tan, Abhishek Sampath, Subhashree Venkatesan, Koiti Inokuchi, Satoshi Wakita, Hiroki Yamaguchi, Wee Joo Chng, Shirley-Kow Yin Kham, Allen Eng-Juh Yeoh, Masashi Sanada, Joanna Schiller, Karl-Anton Kreuzer, Steven M. Kornblau, Hagop M. Kantarjian, Torsten Haferlach, Michael Lill, Ming-Chung Kuo, Lee-Yung Shih, IgorWolfgang Blau, Olga Blau, Henry Yang, Seishi Ogawa, and H. Phillip Koeffler Blood Volume 126(22):2491-2501 November 26, 2015 ©2015 by American Society of Hematology Somatic mutations identified by WES and TDS of FLT3-ITD AML. (A) Number of mutations discovered for 50 individuals at DX, CR, and REL (light gray), 25 individuals at DX and CR (dark gray), and 5 individuals at CR and REL (black). Manoj Garg et al. Blood 2015;126:2491-2501 ©2015 by American Society of Hematology Distribution of somatic mutations in 80 patients with FLT3-ITD AML. Each column displays French-American-British classification, sex, and ethnicity of an individual sample; each row denotes a specific gene. Manoj Garg et al. Blood 2015;126:2491-2501 ©2015 by American Society of Hematology Distribution of mutational nucleotide classes between DX and REL paired samples. Manoj Garg et al. Blood 2015;126:2491-2501 ©2015 by American Society of Hematology Clonal evolution from primary to REL in UPN001 and UPN002 and pattern of evolution observed in 13 DX and REL pairs. Manoj Garg et al. Blood 2015;126:2491-2501 ©2015 by American Society of Hematology MLL3 gene is mutated in FLT3-ITD AML both at DX and REL, and silencing of MLL3 in FLT3-ITD cells increased their growth in both liquid culture and clonogenic assay. Manoj Garg et al. Blood 2015;126:2491-2501 ©2015 by American Society of Hematology MLL3 acts as a recessive gene mutated in FLT3-ITD subgroup. Manoj Garg et al. Blood 2015;126:2491-2501 ©2015 by American Society of Hematology FAT1 and FAT4 somatic mutations in FLT3-ITD AML at DX and REL. (A) Schematic of FAT1 and FAT4 genes with the locations of alterations. Manoj Garg et al. Blood 2015;126:2491-2501 ©2015 by American Society of Hematology