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 Wang; Michael 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

doi:10.1016/j.ccr.2012.10.007

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

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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, …

Cancer cell, Vol.22(5), pp.683-697

2012-11-13

DOI: https://doi.org/10.1016/j.ccr.2012.10.007

PMCID: PMC3547667

PMID: 23153540

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. ► CBFA2T3-GLIS2 is a recurrent fusion gene in pediatric AMKL ► CBFA2T3-GLIS2 AMKL has a distinct expression profile and an inferior outcome ► CBFA2T3-GLIS2 induces BMP signaling and enhanced self-renewal of progenitor cells

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.103 Blood Disorders; 1.103.155 Acute Myeloid Leukemia
Web Of Science research areas: Cell Biology; Oncology
ESI research areas: Molecular Biology & Genetics

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Title: An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia
Creators: Tanja A Gruber - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Amanda Larson Gedman - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Jinghui Zhang - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Cary S Koss - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Suresh Marada - Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Huy Q Ta - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Shann-Ching Chen - Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Xiaoping Su - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Stacey K Ogden - Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Jinjun Dang - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Gang Wu - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Vedant Gupta - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Anna K Andersson - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Stanley Pounds - Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Lei Shi - Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
John Easton - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Michael I Barbato - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Heather L Mulder - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Jayanthi Manne - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Jianmin Wang - Information Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Michael Rusch - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Swati Ranade - Pacific Biosciences, Menlo Park, CA 94025, USA
Ramapriya Ganti - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Matthew Parker - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Jing Ma - Hartwell Center for Biotechnology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Ina Radtke - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Li Ding - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Giovanni Cazzaniga - Centro Ricerca Tettamanti, Pediatric Clinic, University of Milan-Bicocca, 20052 Monza, Italy
Andrea Biondi - Pediatric Unit, University of Milan-Bicocca, San Gerardo Hospital, 20900 Monza, Italy
Steven M Kornblau - Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Farhad Ravandi - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Hagop Kantarjian - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Stephen D Nimer - Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, New York, NY 10065, USA
Konstanze Döhner - Department of Internal Medicine III, University of Ulm, 89081 Ulm, Germany
Hartmut Döhner - Department of Internal Medicine III, University of Ulm, 89081 Ulm, Germany
Timothy J Ley - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Paola Ballerini - Laboratoire d’Hématologie, Hôpital A. Trousseau, 75012 Paris, France
Sheila Shurtleff - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Daisuke Tomizawa - Department of Pediatrics, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Souichi Adachi - Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Yasuhide Hayashi - Department of Haematology/Oncology, Gunma Children’s Medical Center, Shibukawa 377-8577, Japan
Akio Tawa - Department of Pediatrics, National Hospital Organization Osaka National Hospital, Osaka 540-0006, Japan
Lee-Yung Shih - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taipei 105, Taiwan
Der-Cherng Liang - Division of Pediatric Hematology Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan
Jeffrey E Rubnitz - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Ching-Hon Pui - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Elaine R Mardis - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Richard K Wilson - St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
James R Downing - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Publication Details: Cancer cell, Vol.22(5), pp.683-697
Publisher: Elsevier Inc
Academic Unit: Leadership Department; Miller School of Medicine; Sylvester Comprehensive Cancer Center
Language: English
Resource Type: Journal article
PMID: 23153540
PMCID: PMC3547667
Record Identifier: 991031560708702976