Fusion of ZMYND8 and RELA genes in acute erythroid leukemia

Ioannis Panagopoulos; Francesca Micci; Jim Thorsen; Lisbeth Haugom; Jochen Buechner; Gitte Kerndrup; Anne Tierens; Bernward Zeller; Sverre Heim

doi:10.1371/journal.pone.0063663

Fusion of ZMYND8 and RELA genes in acute erythroid leukemia

PLoS One. 2013 May 7;8(5):e63663. doi: 10.1371/journal.pone.0063663. Print 2013.

Authors

Ioannis Panagopoulos¹, Francesca Micci, Jim Thorsen, Lisbeth Haugom, Jochen Buechner, Gitte Kerndrup, Anne Tierens, Bernward Zeller, Sverre Heim

Affiliation

¹ Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ioannis.panagopoulos@rr-research.no

Abstract

Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap. A ZMYND8-RELA fusion was ranked first. RT-PCR and direct sequencing verified the presence of an in frame ZMYND8-RELA chimeric transcript. Fluorescence in situ hybridization showed that the ZMYND8-RELA was located on the p12 band of der(11); therefore a cytogenetically invisible pericentric inversion in chromosome 11 must have taken place besides the translocation. The putative ZMYND8-RELA fusion protein contains the Zinc-PHD finger domain, a bromodomain, a PWWP domain, a MYND type of zinc finger of ZMYND8, and the entire RELA protein, indicating that it might act leukemogenically by influencing several cellular processes including the NF-kappa-B pathway.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Chromosomes, Artificial, Bacterial / genetics
Humans
In Situ Hybridization, Fluorescence
Infant
Leukemia, Erythroblastic, Acute / genetics*
Male
Molecular Sequence Data
Nuclear Proteins / chemistry
Nuclear Proteins / genetics*
Oncogene Proteins, Fusion / chemistry
Oncogene Proteins, Fusion / genetics*
Protein Structure, Tertiary
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor RelA / chemistry
Transcription Factor RelA / genetics*

Substances

Nuclear Proteins
Oncogene Proteins, Fusion
RELA protein, human
Transcription Factor RelA
ZMYND8-RELA fusion protein, human

Grants and funding

The study was supported by grants from the Norwegian Cancer Society and the South-Eastern Norway Regional Health Authority. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.