Next Article in Journal
Deleterious and Oncogenic Mutations in the IL7RA
Previous Article in Journal
Efficacy and Adverse Events in Metastatic Melanoma Patients Treated with Combination BRAF Plus MEK Inhibitors Versus BRAF Inhibitors: A Systematic Review
 
Search for Articles:
Title / Keyword
Author / Affiliation
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
Journals
Cancers
Volume 11
Issue 12
10.3390/cancers11121951
cancers-logo
Submit to this Journal Review for this Journal Edit a Special Issue
► Article Menu

Article Menu

share announcement question_answer thumb_up
...
textsms
...
Article

Novel and Rare Fusion Transcripts Involving Transcription Factors and Tumor Suppressor Genes in Acute Myeloid Leukemia

by
Antonella Padella
1,†,
Giorgia Simonetti
2,†,
Giulia Paciello
3,
George Giotopoulos
4,5,
Carmen Baldazzi
6,
Simona Righi
1,
Martina Ghetti
2,
Anna Stengel
7,
Viviana Guadagnuolo
1,
Rossella De Tommaso
1,
Cristina Papayannidis
1,
Valentina Robustelli
1,
Eugenia Franchini
2,
Andrea Ghelli Luserna di Rorà
2,
Anna Ferrari
2,
Maria Chiara Fontana
1,
Samantha Bruno
1,
Emanuela Ottaviani
1,
Simona Soverini
1,
Clelia Tiziana Storlazzi
8,
Claudia Haferlach
7,
Elena Sabattini
1,
Nicoletta Testoni
1,
Ilaria Iacobucci
9,
Brian J. P. Huntly
4,5,
Elisa Ficarra
3 and
Giovanni Martinelli
2,*add Show full author list remove Hide full author list
1
Department of Experimental, Diagnostic and Speciality Medicine, University of Bologna, 40138 Bologna, Italy
2
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola (FC), Italy
3
Department of Control and Computer Engineering DAUIN, Politecnico di Torino, 10129 Turin, Italy
4
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, UK
5
Department of Haematology, Cambridge Institute for Medical Research and Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0XY, UK
6
Institute of Hematology “L. and A. Seràgnoli”, Sant’Orsola-Malpighi University Hospital, 40138 Bologna, Italy
7
MLL-Munich Leukemia Laboratory, 81377 Munich, Germany
8
Department of Biology, University of Bari Aldo Moro, 70125 Bari, Italy
9
Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
*
Author to whom correspondence should be addressed.
†
A.P. and G.S. contributed equally to this study.
Cancers 2019, 11(12), 1951; https://doi.org/10.3390/cancers11121951
Received: 16 October 2019 / Revised: 15 November 2019 / Accepted: 2 December 2019 / Published: 5 December 2019
View Full-Text Download PDF
Browse Figures

Abstract

Approximately 18% of acute myeloid leukemia (AML) cases express a fusion transcript. However, few fusions are recurrent across AML and the identification of these rare chimeras is of interest to characterize AML patients. Here, we studied the transcriptome of 8 adult AML patients with poorly described chromosomal translocation(s), with the aim of identifying novel and rare fusion transcripts. We integrated RNA-sequencing data with multiple approaches including computational analysis, Sanger sequencing, fluorescence in situ hybridization and in vitro studies to assess the oncogenic potential of the ZEB2-BCL11B chimera. We detected 7 different fusions with partner genes involving transcription factors (OAZ-MAFK, ZEB2-BCL11B), tumor suppressors (SAV1-GYPB, PUF60-TYW1, CNOT2-WT1) and rearrangements associated with the loss of NF1 (CPD-PXT1, UTP6-CRLF3). Notably, ZEB2-BCL11B rearrangements co-occurred with FLT3 mutations and were associated with a poorly differentiated or mixed phenotype leukemia. Although the fusion alone did not transform murine c-Kit+ bone marrow cells, 45.4% of 14q32 non-rearranged AML cases were also BCL11B-positive, suggesting a more general and complex mechanism of leukemogenesis associated with BCL11B expression. Overall, by combining different approaches, we described rare fusion events contributing to the complexity of AML and we linked the expression of some chimeras to genomic alterations hitting known genes in AML. View Full-Text
Keywords: acute myeloid leukemia; rare fusion genes; ZEB2-BCL11B acute myeloid leukemia; rare fusion genes; ZEB2-BCL11B
►▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

SciFeed

Share and Cite

MDPI and ACS Style

Padella, A.; Simonetti, G.; Paciello, G.; Giotopoulos, G.; Baldazzi, C.; Righi, S.; Ghetti, M.; Stengel, A.; Guadagnuolo, V.; De Tommaso, R.; Papayannidis, C.; Robustelli, V.; Franchini, E.; Ghelli Luserna di Rorà, A.; Ferrari, A.; Fontana, M.C.; Bruno, S.; Ottaviani, E.; Soverini, S.; Storlazzi, C.T.; Haferlach, C.; Sabattini, E.; Testoni, N.; Iacobucci, I.; Huntly, B.J.P.; Ficarra, E.; Martinelli, G. Novel and Rare Fusion Transcripts Involving Transcription Factors and Tumor Suppressor Genes in Acute Myeloid Leukemia. Cancers 2019, 11, 1951. https://doi.org/10.3390/cancers11121951

AMA Style

Padella A, Simonetti G, Paciello G, Giotopoulos G, Baldazzi C, Righi S, Ghetti M, Stengel A, Guadagnuolo V, De Tommaso R, Papayannidis C, Robustelli V, Franchini E, Ghelli Luserna di Rorà A, Ferrari A, Fontana MC, Bruno S, Ottaviani E, Soverini S, Storlazzi CT, Haferlach C, Sabattini E, Testoni N, Iacobucci I, Huntly BJP, Ficarra E, Martinelli G. Novel and Rare Fusion Transcripts Involving Transcription Factors and Tumor Suppressor Genes in Acute Myeloid Leukemia. Cancers. 2019; 11(12):1951. https://doi.org/10.3390/cancers11121951

Chicago/Turabian Style

Padella, Antonella, Giorgia Simonetti, Giulia Paciello, George Giotopoulos, Carmen Baldazzi, Simona Righi, Martina Ghetti, Anna Stengel, Viviana Guadagnuolo, Rossella De Tommaso, Cristina Papayannidis, Valentina Robustelli, Eugenia Franchini, Andrea Ghelli Luserna di Rorà, Anna Ferrari, Maria C. Fontana, Samantha Bruno, Emanuela Ottaviani, Simona Soverini, Clelia T. Storlazzi, Claudia Haferlach, Elena Sabattini, Nicoletta Testoni, Ilaria Iacobucci, Brian J.P. Huntly, Elisa Ficarra, and Giovanni Martinelli. 2019. "Novel and Rare Fusion Transcripts Involving Transcription Factors and Tumor Suppressor Genes in Acute Myeloid Leukemia" Cancers 11, no. 12: 1951. https://doi.org/10.3390/cancers11121951

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Map by Country/Region

1
Back to TopTop