July 7, 2019  |  

An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.

Authors: Gruber, Tanja A and Larson Gedman, Amanda and Zhang, Jinghui and Koss, Cary S and Marada, Suresh and Ta, Huy Q and Chen, Shann-Ching and Su, Xiaoping and Ogden, Stacey K and Dang, Jinjun and Wu, Gang and Gupta, Vedant and Andersson, Anna K and Pounds, Stanley and Shi, Lei and Easton, John and Barbato, Michael I and Mulder, Heather L and Manne, Jayanthi and Wang, Jianmin and Rusch, Michael and Ranade, Swati and Ganti, Ramapriya and Parker, Matthew and Ma, Jing and Radtke, Ina and Ding, Li and Cazzaniga, Giovanni and Biondi, Andrea and Kornblau, Steven M and Ravandi, Farhad and Kantarjian, Hagop and Nimer, Stephen D and Döhner, Konstanze and Döhner, Hartmut and Ley, Timothy J and Ballerini, Paola and Shurtleff, Sheila and Tomizawa, Daisuke and Adachi, Souichi and Hayashi, Yasuhide and Tawa, Akio and Shih, Lee-Yung and Liang, Der-Cherng and Rubnitz, Jeffrey E and Pui, Ching-Hon and Mardis, Elaine R and Wilson, Richard K and Downing, James R

To define the mutation spectrum in non-Down syndrome acute megakaryoblastic 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 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. Copyright © 2012 Elsevier Inc. All rights reserved.

Journal: Cancer cell
DOI: 10.1016/j.ccr.2012.10.007
Year: 2012

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