An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia

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

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)683-697
Number of pages15
JournalCancer Cell
Volume22
Issue number5
DOIs
StatePublished - Nov 13 2012

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Gruber, T. A., Larson Gedman, A., Zhang, J., Koss, C. S., Marada, S., Ta, H. Q., Chen, S. C., Su, X., Ogden, S. K., Dang, J., Wu, G., Gupta, V., Andersson, A. K., Pounds, S., Shi, L., Easton, J., Barbato, M. I., Mulder, H. L., Manne, J., ... Downing, J. R. (2012). An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia. Cancer Cell, 22(5), 683-697. https://doi.org/10.1016/j.ccr.2012.10.007