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

111 Citations (Scopus)

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

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Leukemia, Megakaryoblastic, Acute
Pediatrics
Chromosomes, Human, Pair 16
Proteins
Transcriptome
Drosophila
Bone and Bones
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Gruber, T. A., Larson Gedman, A., Zhang, J., Koss, C. S., Marada, S., Ta, H. Q., ... 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

An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia. / Gruber, Tanja A.; Larson Gedman, Amanda; Zhang, Jinghui; Koss, Cary S.; Marada, Suresh; Ta, Huy Q.; Chen, Shann Ching; Su, Xiaoping; Ogden, Stacey K.; Dang, Jinjun; Wu, Gang; Gupta, Vedant; Andersson, Anna K.; Pounds, Stanley; Shi, Lei; Easton, John; Barbato, Michael I.; Mulder, Heather L.; Manne, Jayanthi; Wang, Jianmin; Rusch, Michael; Ranade, Swati; Ganti, Ramapriya; Parker, Matthew; Ma, Jing; Radtke, Ina; Ding, Li; Cazzaniga, Giovanni; Biondi, Andrea; Kornblau, Steven M.; Ravandi, Farhad; Kantarjian, Hagop; Nimer, Stephen D; Döhner, Konstanze; Döhner, Hartmut; Ley, Timothy J.; Ballerini, Paola; Shurtleff, Sheila; Tomizawa, Daisuke; Adachi, Souichi; Hayashi, Yasuhide; Tawa, Akio; Shih, Lee Yung; Liang, Der Cherng; Rubnitz, Jeffrey E.; Pui, Ching Hon; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.

In: Cancer Cell, Vol. 22, No. 5, 13.11.2012, p. 683-697.

Research output: Contribution to journalArticle

Gruber, TA, Larson Gedman, A, Zhang, J, Koss, CS, Marada, S, Ta, HQ, Chen, SC, Su, X, Ogden, SK, Dang, J, Wu, G, Gupta, V, Andersson, AK, Pounds, S, Shi, L, Easton, J, Barbato, MI, Mulder, HL, Manne, J, Wang, J, Rusch, M, Ranade, S, Ganti, R, Parker, M, Ma, J, Radtke, I, Ding, L, Cazzaniga, G, Biondi, A, Kornblau, SM, Ravandi, F, Kantarjian, H, Nimer, SD, Döhner, K, Döhner, H, Ley, TJ, Ballerini, P, Shurtleff, S, Tomizawa, D, Adachi, S, Hayashi, Y, Tawa, A, Shih, LY, Liang, DC, Rubnitz, JE, Pui, CH, Mardis, ER, Wilson, RK & Downing, JR 2012, 'An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia', Cancer Cell, vol. 22, no. 5, pp. 683-697. https://doi.org/10.1016/j.ccr.2012.10.007
Gruber, Tanja A. ; Larson Gedman, Amanda ; Zhang, Jinghui ; Koss, Cary S. ; Marada, Suresh ; Ta, Huy Q. ; Chen, Shann Ching ; Su, Xiaoping ; Ogden, Stacey K. ; Dang, Jinjun ; Wu, Gang ; Gupta, Vedant ; Andersson, Anna K. ; Pounds, Stanley ; Shi, Lei ; Easton, John ; Barbato, Michael I. ; Mulder, Heather L. ; Manne, Jayanthi ; Wang, Jianmin ; Rusch, Michael ; Ranade, Swati ; Ganti, Ramapriya ; Parker, Matthew ; Ma, Jing ; Radtke, Ina ; Ding, Li ; Cazzaniga, Giovanni ; Biondi, Andrea ; Kornblau, Steven M. ; Ravandi, Farhad ; Kantarjian, Hagop ; Nimer, Stephen D ; Döhner, Konstanze ; Döhner, Hartmut ; Ley, Timothy J. ; Ballerini, Paola ; Shurtleff, Sheila ; Tomizawa, Daisuke ; Adachi, Souichi ; Hayashi, Yasuhide ; Tawa, Akio ; Shih, Lee Yung ; Liang, Der Cherng ; Rubnitz, Jeffrey E. ; Pui, Ching Hon ; Mardis, Elaine R. ; Wilson, Richard K. ; Downing, James R. / An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia. In: Cancer Cell. 2012 ; Vol. 22, No. 5. pp. 683-697.
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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.",
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AU - Gruber, Tanja A.

AU - Larson Gedman, Amanda

AU - Zhang, Jinghui

AU - Koss, Cary S.

AU - Marada, Suresh

AU - Ta, Huy Q.

AU - Chen, Shann Ching

AU - Su, Xiaoping

AU - Ogden, Stacey K.

AU - Dang, Jinjun

AU - Wu, Gang

AU - Gupta, Vedant

AU - Andersson, Anna K.

AU - Pounds, Stanley

AU - Shi, Lei

AU - Easton, John

AU - Barbato, Michael I.

AU - Mulder, Heather L.

AU - Manne, Jayanthi

AU - Wang, Jianmin

AU - Rusch, Michael

AU - Ranade, Swati

AU - Ganti, Ramapriya

AU - Parker, Matthew

AU - Ma, Jing

AU - Radtke, Ina

AU - Ding, Li

AU - Cazzaniga, Giovanni

AU - Biondi, Andrea

AU - Kornblau, Steven M.

AU - Ravandi, Farhad

AU - Kantarjian, Hagop

AU - Nimer, Stephen D

AU - Döhner, Konstanze

AU - Döhner, Hartmut

AU - Ley, Timothy J.

AU - Ballerini, Paola

AU - Shurtleff, Sheila

AU - Tomizawa, Daisuke

AU - Adachi, Souichi

AU - Hayashi, Yasuhide

AU - Tawa, Akio

AU - Shih, Lee Yung

AU - Liang, Der Cherng

AU - Rubnitz, Jeffrey E.

AU - Pui, Ching Hon

AU - Mardis, Elaine R.

AU - Wilson, Richard K.

AU - Downing, James R.

PY - 2012/11/13

Y1 - 2012/11/13

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