1. An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia
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Timothy J. Ley, James R. Downing, Xiaoping Su, Andrea Biondi, Jianmin Wang, Li Ding, Stanley Pounds, Tanja A. Gruber, Matthew Parker, Der Cherng Liang, Heather L. Mulder, Giovanni Cazzaniga, Jeffrey E. Rubnitz, Michael Rusch, Paola Ballerini, John Easton, Hartmut Döhner, Ching-Hon Pui, Ramapriya Ganti, Michael I. Barbato, Sheila A. Shurtleff, Farhad Ravandi, Jinghui Zhang, Richard K. Wilson, Yasuhide Hayashi, Lee Yung Shih, Huy Q. Ta, Ina Radtke, Steven M. Kornblau, Stacey K. Ogden, Amanda Larson Gedman, Anna Andersson, Daisuke Tomizawa, Jayanthi Manne, Vedant Gupta, Swati Ranade, Akio Tawa, Stephen D. Nimer, Shann Ching Chen, Gang Wu, Souichi Adachi, Konstanze Döhner, Lei Shi, Jing Ma, Suresh Marada, Jinjun Dang, Elaine R. Mardis, Hagop M. Kantarjian, Cary Koss, Gruber, T, Larson Gedman, A, Zhang, J, Koss, C, Marada, S, Ta, H, Chen, S, Su, X, Ogden, S, Dang, J, Wu, G, Gupta, V, Andersson, A, Pounds, S, Sh, L, Easton, J, Barbato, M, Mulder, H, Manne, J, Wang, J, Rusch, M, Ranade, S, Ganti, R, Parker, M, Ma, J, Radtke, I, Ding, L, Cazzaniga, G, Biondi, A, Kornblau, S, Ravandi, F, Kantarjian, H, Nimer, S, Döhner, K, Döhner, H, Ley, T, Ballerini, P, Shurtleff, S, Tomizawa, D, Adachi, S, Hayashi, Y, Tawa, A, Shih, L, Liang, D, Rubnitz, J, Pui, C, Mardis, E, Wilson, R, and Downing, J
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0303 health sciences ,Mutation ,Cancer Research ,Cell Biology ,Biology ,medicine.disease_cause ,medicine.disease ,Bone morphogenetic protein ,Fusion protein ,Molecular biology ,Article ,3. Good health ,Gene expression profiling ,03 medical and health sciences ,Acute megakaryoblastic leukemia ,Haematopoiesis ,0302 clinical medicine ,Chromosome 16 ,AML ,Oncology ,030220 oncology & carcinogenesis ,medicine ,030304 developmental biology ,Chromosomal inversion - Abstract
To define the mutation spectrum in non-Down syndrome acute megkaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL leukemia samples. Our analysis identified a cryptic chromosome 16 inversion [inv(16)(p13.3q24.3)] in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2 fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling, and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors. These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis.
- Published
- 2012
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