Novel and rare fusion transcripts involving transcription factors and tumor suppressor genes in acute myeloid leukemia

Antonella Padella, 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 Chiara Fontana, Samantha Bruno, Emanuela Ottaviani, Simona Soverini, Clelia Tiziana StorlazziClaudia Haferlach, Elena Sabattini, Nicoletta Testoni, Ilaria Iacobucci, Brian J.P. Huntly, Elisa Ficarra, Giovanni Martinelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1951
JournalCancers
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Acute myeloid leukemia
  • Rare fusion genes
  • ZEB2-BCL11B

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Novel and rare fusion transcripts involving transcription factors and tumor suppressor genes in acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this