An inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia Journal Article
| Authors: | 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.; Wang, J.; Rusch, M.; Ranade, S.; Ganti, R.; Parker, M.; Ma, J.; Radtke, I.; Ding, L.; Cazzaniga, G.; Biondi, A.; Kornblau, S. M.; Ravandi, F.; Kantarjian, H.; Nimer, S. D.; Döhner, K.; Döhner, H.; Ley, T. J.; Ballerini, P.; Shurtleff, S.; Tomizawa, D.; Adachi, S.; Hayashi, Y.; Tawa, A.; Shih, L. Y.; Liang, D. C.; Rubnitz, J. E.; Pui, C. H.; Mardis, E. R.; Wilson, R. K.; Downing, J. R. |
| Article Title: | An inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia |
| 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. © 2012 Elsevier Inc. |
| Keywords: | signal transduction; adult; child; clinical article; controlled study; protein expression; unclassified drug; gene mutation; gene sequence; animals; mice; gene expression profiling; bone morphogenetic protein; drosophila; cell renewal; validation study; hybrid protein; recombinant fusion proteins; nucleotide sequence; leukemogenesis; tumor suppressor proteins; oncogene proteins, fusion; kruppel-like transcription factors; hematopoietic cell; sequence analysis, rna; repressor proteins; transcriptome; bone morphogenetic proteins; chromosome 16p; chromosomes, human, pair 16; chromosome inversion; acute megakaryocytic leukemia; cbfa2t3 glis2 fusion protein; chromosome inversion 16; leukemia, megakaryoblastic, acute |
| Journal Title: | Cancer Cell |
| Volume: | 22 |
| Issue: | 5 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2012-11-13 |
| Start Page: | 683 |
| End Page: | 697 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2012.10.007 |
| PROVIDER: | scopus |
| PUBMED: | 23153540 |
| PMCID: | PMC3547667 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 December 2012" - "CODEN: CCAEC" - "Source: Scopus" |
